The DOI matches its Crossref record; 232 of the 236 references it cites were found in a registry or an index; 146 of the 190 sources its claims cite were checked for support.
Tumor microenvironment complexity and therapeutic implications at a glance
Open accessAbstract
The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices. Video abstract.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
50 Supported · 47 Partly supported · 19 No full text of the sources · 14 Own interpretation · 6 Supported so far · 6 Couldn’t confirm · 5 Not supported · 4 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Chemotherapeutic agents can also be targeted to ECM of the tumor cells through the membrane-bound receptors such as tenascin-C [132].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Disputedcites [132] Raavé R, van Kuppevelt TH, Daamen WF. Chemotherapeutic drug delivery by tumoral extracellular matrix targeting. J Control Release. 2018;274:1–8. sourceExperimental — accuracy not yet measured
Section 4, “Alternative tumor targeting strategy,” explicitly says ECM targeting is not aimed at membrane-bound receptors on tumor cells. Section 4.2 identifies tenascin-C as a glycoprotein in the tumor ECM that can be targeted to deliver a chemotherapeutic compound, not as a membrane-bound receptor. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Importantly, combination treatment with CPI and IL-2 resulted in complete elimination of tumors in a considerable number of animals (9 of 13) bearing orthotopic breast cancer [137].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Disputedcites [137] Ishihara J, Ishihara A, Sasaki K, Lee SS-Y, Williford J-M, Yasui M, Abe H, Potin L, Hosseinchi P, Fukunaga K, et al. Targeted antibody and cytokine cancer immunotherapies through collagen affinity. Sci Transl Med. 2019;11:eaau3259. sourceExperimental — accuracy not yet measured
The Results section distinguishes the two combinations: CBD-CPI plus CBD-IL-2 produced complete remission in 9 of 13 mice with MMTV-PyMT breast tumors, whereas unmodified CPI plus IL-2 did so in only 1 of 13. The cited sentence assigns the 9-of-13 result to CPI plus IL-2 without the essential CBD modification. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
plaindirectn = 13- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“LOX enzymes are widely used to block collagen crosslinking in various preclinical settings [130, 131].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Not checked — no full text of the sourcecites [130] Hajdú I, Kardos J, Major B, Fabó G, Lőrincz Z, Cseh S, Dormán G. Inhibition of the LOX enzyme family members with old and new ligands. Selectivity analysis revisited. Bioorg Med Chem Lett. 2018;28:3113–8. source
- Disputedcites [131] Puente A, Fortea JI, Cabezas J, Arias Loste MT, Iruzubieta P, Llerena S, Huelin P, Fábrega E, Crespo J. LOXL2—a new target in Antifibrogenic therapy? Int J Mol Sci. 2019;20:1634. sourceExperimental — accuracy not yet measured
Section 3, “Fibrosis Reversion—Lysyl Oxidase 2” (page not provided), says LOXL2 promotes collagen crosslinks, rather than blocking them. It describes preclinical use of an antibody that inhibits LOXL2—not use of LOX enzymes to block crosslinking. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“These include circulating tumor cells (CTCs), exosomes, cell-free DNA (cfDNA) and apoptotic bodies as novel horizontal gene transfer (HGT) mediators derived from tumor cells and delivering information to distant target cells including tumor cells and/or normal cells [6, 7].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
What the sources say
- Could not verifycites [6] Denisenko TV, Budkevich IN, Zhivotovsky BJCd, disease: Cell death-based treatment of lung adenocarcinoma. 2018, 9:117. sourceExperimental — accuracy not yet measured
The Combination therapies section discusses communication between malignant and neighboring nonmalignant cells through cytokines, chemokines, growth factors, and enzymes, but does not describe horizontal gene transfer. Searches for circulating tumor cells, exosomes, cell-free DNA, and apoptotic bodies found no passage identifying them as mediators that deliver information to distant cells. No page number was available in our copy. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [7] Balkwill FR, Capasso M, Hagemann T: The tumor microenvironment at a glance. The Company of Biologists Ltd; 2012. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Pericytes are vital multifunctional cells in TME that envelop the surface of endothelial cells using cytoplasmic processes that extend along the abluminal surface of the endothelium [23].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Pericytes
What the sources say
- Could not verifycites [23] Abbasi MM, Helli S, Monfaredan A, Jahanban-Esfahlan R. Hesa-a improves clinical outcome of Oral carcinoma by affecting p53 gene expression in vivo. Asian Pac J Cancer Prev. 2015;16:4169–72. sourceExperimental — accuracy not yet measured
The Introduction and Discussion address Hesa-A treatment and p53 expression in oral carcinoma, not pericytes. Searches for pericytes, their cytoplasmic processes, and their relationship to endothelial cells found no passage addressing the cited claim. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Along with endothelial cells, pericytes are involved in the basement membrane remodeling during angiogenesis [24] and tumorigenesis [25].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Pericytes
What the sources say
- Supportedcites [24] Kloc M, Kubiak JZ, Li XC, Ghobrial RM. Pericytes, microvasular dysfunction and chronic rejection. Transplantation. 2015;99:658. source
The citation following “angiogenesis” is supported by the section “Pericyte localization, structure and markers,” which says endothelial cells produce an immature basement membrane and recruited pericytes co-participate in its maturation. The separate tumorigenesis clause has its own citation and is not assessed against this source. (LLM, conf=0.91)
- Supportedcites [25] Baluk P, Morikawa S, Haskell A, Mancuso M, McDonald DM. Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Am J Pathol. 2003;163:1801–15. source
The introduction (Am J Pathol 2003, pp. 1801–1815) describes vascular basement membrane as formed by endothelial cells and pericytes. In “Basement Membrane on Endothelial Sprouts,” the authors report that pericytes contribute to basement membrane synthesis and were associated with most sprouts they observed in tumors, supporting their involvement in remodeling of tumor vessels. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The process of tumor formation and progression is influenced by two factors, namely genetic/epigenetic changes in the tumor cells and the rearrangement of the components of the tumor microenvironment (TME) through mutual and dynamic crosstalk [1].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
What the sources say
- Could not verifycites [1] Jahanban-Esfahlan R, Seidi K, Monhemi H, Adli ADF, Minofar B, Zare P, Farajzadeh D, Farajnia S, Behzadi R, Abbasi MM, et al. RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice. Sci Rep. 2017;7:8126. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) notes that implanted tumors can have different microenvironments and interactions with stroma, but it does not say that genetic or epigenetic changes and dynamic crosstalk rearranging microenvironment components drive tumor formation and progression. Searches for those terms found no passage in our copy addressing that account. (LLM, conf=0.72)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Recent advances on three dimensional (3D) platforms through the use of lab-on-chip and microfluidic devices [17] have provided an enormous opportunity to better stimulate the function and biology of TME and to bridge the translational gap between preclinical and clinical settings [18].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
What the sources say
- Not checked — no full text of the sourcecites [17] Ayubi Joshagani MH, Dianat-Moghadam H, Seidi K, Jahanban-Esfahlan A, Zare P, Jahanban-Esfahlan R. Cell-free protein synthesis: the transition from batch reactions to minimal cells and microfluidic devices. Biotechnol Bioeng. 2019;117:1204–29. source
- Supportedcites [18] Sleeboom JJF, Eslami Amirabadi H, Nair P, Sahlgren CM, den Toonder JMJ. Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches. Disease Models Mechanisms. 2018;11:dmm033100. source
The Introduction describes microfluidic cancer-on-a-chip models that reproduce and control features of the tumor microenvironment, including 3D cultures. The Conclusion says these models could reduce reliance on animal models and, when combined with clinical material, help investigate patient-specific cancer progression and test drug efficacy. That supports the claimed opportunity to improve TME modeling and connect preclinical work with clinical applications; it does not claim the gap has already been closed. (LLM, conf=0.87)
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In vitro 3D and microfluidic models sufficiently recapitulate the in vivo tumor microenvironment to inform therapeutic development.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The loss of tissue integrity, carcinogenesis and further progress occurs as a consequence of reciprocal interactions between tumor cells with non-cellular (ECM) and cellular components of the TME [9, 10].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
What the sources say
- Partly supportedcites [9] Jahanban-Esfahlan R, Seidi K, Manjili MH, Jahanban-Esfahlan A, Javaheri T, Zare P. Tumor cell dormancy: threat or opportunity in the fight against Cancer. Cancers. 2019;11:1207. sourceExperimental — accuracy not yet measured
Section 5, “ECM Remodeling” (page unavailable), links tumor-cell interactions with the ECM to metastatic outgrowth. Section 3, “Cancer Immune-Mediated Dormancy” (page unavailable), describes interactions with stromal and immune cells that can affect cancer growth. These passages support the progression aspect, but do not establish that those interactions cause loss of tissue integrity or carcinogenesis. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [10] Seidi K, Neubauer HA, Moriggl R, Jahanban-Esfahlan R, Javaheri T. Tumor target amplification: implications for nano drug delivery systems. J Control Release. 2018;275:142–61. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Therefore, on the other side of the argument, interactions in reactive non-neoplastic cells, genetically-altered tumor cells, and ECM control the majority of the stages of tumorigenesis effectively including clonal evolution, cancer heterogeneity, epithelial-mesenchymal-transition (EMT), migration, invasion, development of metastasis, neovascularization, apoptosis and chemotherapeutic drug resist”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
What the sources say
- Partly supportedcites [11] Ungefroren H, Sebens S, Seidl D, Lehnert H, Hass R. Interaction of tumor cells with the microenvironment. Cell CommunSignaling. 2011;9:18. sourceExperimental — accuracy not yet measured
The Abstract states that interactions among genetically altered tumor cells, reactive non-neoplastic cells, and the ECM control most aspects of tumorigenesis, and lists EMT, migration, invasion, metastasis, neovascularization, apoptosis, and chemotherapeutic drug resistance. It does not include clonal evolution or cancer heterogeneity; searches for those terms found no supporting passage in our copy. No page number is provided. (LLM, conf=0.90)
- Partly supportedcites [12] Li W, Ng JM-K, Wong CC, Ng EKW, Yu JJO: Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer 2018:1. sourceExperimental — accuracy not yet measured
The Stromal environment and Local invasion sections (page not available in our copy) describe cross-talk between gastric cancer cells and stroma, and link EMT, ECM-related processes, and stromal interactions to invasion and progression. The paper does not support the stronger claim that these interactions control most stages of tumorigenesis, particularly clonal evolution, cancer heterogeneity, and chemotherapeutic drug resistance. (LLM, conf=0.87)
- Partly supportedcites [13] Tsao AS, Scagliotti GV, Bunn Jr PA, Carbone DP, Warren GW, Bai C, De Koning HJ, Yousaf-Khan AU, McWilliams A, Tsao MSJJoTO: Scientific advances in lung cancer 2015. 2016, 11:613–638. sourceExperimental — accuracy not yet measured
The Hirsch section (page unavailable) says that interactions between malignant and neighboring nonmalignant cells create a dynamic tumor microenvironment, and it mentions matrix-remodeling enzymes. It does not say that those interactions control the majority of tumorigenesis stages or establish the claimed list of effects, including clonal evolution, EMT, metastasis, and chemotherapy resistance. (LLM, conf=0.84)
- Partly supportedcites [14] Cova TF, Bento DJ, Nunes SC. Computational approaches in Theranostics: mining and predicting Cancer data. Pharmaceutics. 2019;11:119. sourceExperimental — accuracy not yet measured
The Introduction (page not available) says that interactions between cells and their surrounding medium affect cancer growth and tissue invasion. Section 2 (page not available) also discusses tumor heterogeneity, angiogenesis, and drug resistance. But the copy does not say that interactions among reactive non-neoplastic cells, genetically altered tumor cells, and ECM control the majority of the listed stages of tumorigenesis; several listed stages, including clonal evolution and epithelial–mesenchymal transition, are not established by these passages. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- It may state two separate claims as one. 49
- Probably not a substantial claim. 6
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Besides, exosomes are involved in acquired drug resistance, as evidenced by the observation that the transfer of the oncogene MET by exosomes modify surrounding icotinib-sensitive cells to promote icotinib-resistant lung cancer cells, that produce MET-containing exosomes and elicit the migration and invasion properties in vitro [175].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Disputedcites [175] Yu Y, Abudula M, Li C, Chen Z, Zhang Y, Chen Y. Icotinib-resistant HCC827 cells produce exosomes with mRNA MET oncogenes and mediate the migration and invasion of NSCLC. Respir Res. 2019;20:217. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Mechanistically, miR-122 downregulate the glycolytic enzyme pyruvate kinase and restores glucose uptake by lungs and brain and lessen disease progression [177].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Disputedcites [177] Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, Chow A, O’Connor STF, Li S, Chin ARJNcb: Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17:183–94. sourceExperimental — accuracy not yet measured
The Results section confirms that miR-122 downregulates pyruvate kinase, but reports that miR-122 reduces glucose uptake by niche cells and promotes metastasis—the opposite of the claimed effects. In “Systemic miR-122 intervention,” inhibiting miR-122 reduced the incidence of brain and lung metastasis and alleviated suppressed glucose uptake in the brain; restoration of uptake in the lungs was not significant. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Abstract
What the sources say
- Could not verifycites [1] Jahanban-Esfahlan R, Seidi K, Monhemi H, Adli ADF, Minofar B, Zare P, Farajzadeh D, Farajnia S, Behzadi R, Abbasi MM, et al. RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice. Sci Rep. 2017;7:8126. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While several studies have shown that greater pericytes coverage corresponds to a better diagnosis [30]”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Pericytes
What the sources say
- Partly supportedcites [30] Mezheyeuski A, Lindh MB, Guren TK, Dragomir A, Pfeiffer P, Kure EH, Ikdahl T, Skovlund E, Corvigno S, Strell C. Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer. Oncotarget. 2016;7:41948. sourceExperimental — accuracy not yet measured
The Results (page unavailable) associate greater PDGFR-β-defined vessel coverage with longer overall survival in patients with metastatic colorectal cancer. The claim is broader than that finding: the paper does not establish that greater pericyte coverage generally predicts a better prognosis, and its Discussion notes opposite associations in some other cancers. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, gold NPs block VEGF-VEGFR2 signaling from TME cells to endothelial cells and inhibit angiogenesis as reflected in reduced migration and tube formation of ECs when co-cultured with TCs in vitro [52].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Partly supportedcites [52] Zhang Y, Xiong X, Huai Y, Dey A, Hossen MN, Roy RV, Elechalawar CK, Rao G, Bhattacharya R, Mukherjee P. Gold nanoparticles disrupt tumor microenvironment - endothelial cell cross talk to inhibit Angiogenic phenotypes in vitro. Bioconjug Chem. 2019;30:1724–33. sourceExperimental — accuracy not yet measured
The Discussion reports that gold nanoparticles reduced VEGF-dependent VEGFR2 signaling and inhibited endothelial angiogenic phenotypes in vitro. The Results show reduced endothelial migration in co-culture with treated tumor cells, but the tube-formation assay used conditioned media rather than co-culture; that experimental detail in the claim is not supported. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“3D spheroids have provided a more reliable physiological environment for studying the interaction of TECs with tumor stroma, where the shape and surface texture of the spheroids indicates spatial invasiveness of cells in ECM [55].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Partly supportedcites [55] Shoval H, Karsch-Bluman A, Brill-Karniely Y, Stern T, Zamir G, Hubert A, Benny O. Tumor cells and their crosstalk with endothelial cells in 3D spheroids. Sci Rep. 2017;7:10428. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says hybrid 3D spheroids model tumor–endothelial interactions and that spheroid shape and surface texture may indicate spatial invasiveness in ECM. The claim is stronger than the paper’s tentative finding, and the study used human umbilical vein endothelial cells (HUVEC), not endothelial cells isolated from tumors (TECs). (LLM, conf=0.87)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The results indicated inhibitory role of adenosine on extravasation as blocking A3 adenosine receptors increased extravasation rates of breast cancer cells into the myoblast, mimicking microenvironments compared with untreated cells [57].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Supportedcites [57] Jeon JS, Bersini S, Gilardi M, Dubini G, Charest JL, Moretti M, Kamm RD. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proc Natl Acad Sci U S A. 2015;112:214–9. source
The Results (p. 5) report that blocking A3 adenosine receptors increased breast cancer cell extravasation in C2C12 muscle-mimicking matrices from 8.2 ± 2.3% untreated to 32.4 ± 7.7%. The paper interprets this as evidence of a protective role for adenosine against extravasation. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“As outstanding components of TME, TECs not only support the tumor with nutrients but also influence the immune cell infiltration and tumor’s stromal cell arrangement [47].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Could not verifycites [47] Abbasi MM, Mehdipour M, Monfaredan A, Jahanban-Esfahlan R. Hesa-a Down-regulates erb/b2 oncogene expression and improves outcome of Oral carcinoma in a rat model. Asian Pac J Cancer Prev. 2015;16:6947–51. sourceExperimental — accuracy not yet measured
The Introduction and Discussion address Hesa-A treatment and erb/b2 expression in a rat model of oral carcinoma, not the functions of tumor endothelial cells (TECs). Searches for TECs, nutrient supply, immune-cell infiltration, and stromal arrangement found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, 3D microfluidic system has enabled a high resolution, real-time imaging, and precise quantification of endothelial barrier function, which is essential for investigating the interaction of tumor cells during the metastasis process.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Supportedcites [56] Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci. 2012;109:13515–20. source
The Abstract says the 3D microfluidic assay allows high-resolution, real-time imaging and precise quantification of endothelial barrier function. The Discussion says it uses these capabilities to investigate tumor–endothelial interactions during intravasation, a step in metastasis. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These properties promote the tumor cell heterogeneity, cancer resistance and impair efficient drug delivery [2, 8, 46].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Not checked — no full text of the sourcecites [2] Jahanban-Esfahlan R, Seidi K, Banimohamad-Shotorbani B, Jahanban-Esfahlan A, Yousefi B. Combination of nanotechnology with vascular targeting agents for effective cancer therapy. J Cell Physiol. 2017;233:2982–92. source
- Not checked — no full text of the sourcecites [8] Jahanban-Esfahlan R, de la Guardia M, Ahmadi D, Yousefi B. Modulating tumor hypoxia by nanomedicine for effective cancer therapy. J Cell Physiol. 2017;233:2019–31. source
- Partly supportedcites [46] Abdalla AME, Xiao L, Ullah MW, Yu M, Ouyang C, Yang G. Current challenges of Cancer anti-angiogenic therapy and the promise of Nanotherapeutics. Theranostics. 2018;8:533–48. sourceExperimental — accuracy not yet measured
The section “Abnormality of tumor vessels and their microenvironment” (page unavailable) says abnormal vessels and physiological barriers impede delivery of therapeutic agents, and that hypoxia arising from impaired blood supply mediates drug resistance. It describes gradients in proliferation, hypoxia and acidity, but does not say these properties promote tumor cell heterogeneity. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TECs contain stem cell-like populations and overexpress MDR1 and aldehyde dehydrogenase (ALDH) and become resistant to chemotherapeutics such as paclitaxel and 5-fluorouracil in vitro [43, 44].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Partly supportedcites [43] Akiyama K, Ohga N, Hida Y, Kawamoto T, Sadamoto Y, Ishikawa S, Maishi N, Akino T, Kondoh M, Matsuda A, et al. Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol. 2012;180:1283–93. sourceExperimental — accuracy not yet measured
The section “TECs Are Resistant to Anticancer Drugs” reports higher MDR1 expression and greater paclitaxel resistance in TECs than in normal endothelial cells. The introductory passage reports 5-fluorouracil resistance in hepatocellular carcinoma endothelial cells, but this paper does not establish that the studied TECs resist 5-fluorouracil. The passages do not support the stem cell-like population or ALDH-overexpression claims. (LLM, conf=0.87)
- Supportedcites [44] Hida K, Maishi N, Akiyama K, Ohmura-Kakutani H, Torii C, Ohga N, Osawa T, Kikuchi H, Morimoto H, Morimoto M, et al. Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance. Cancer Sci. 2017;108:2195–203. source
The paper describes stem cell-like TEC populations and elevated ALDH activity (p. 2). The Discussion (p. 8) reports paclitaxel resistance in a TEC subgroup with ABCB1/MDR1 upregulation, while the Results (p. 6) show that ALDH-high TEC resist 5-fluorouracil in vitro. These are distinct reported findings, rather than evidence that both markers confer resistance to both drugs. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TECs are not only involved in the angiogenesis process to support primary tumor growth, but also promote tumor progression, metastasis and drug resistance [41].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Partly supportedcites [41] Dudley AC. Tumor endothelial cells. Cold Spring Harbor perspectives in medicine. 2012;2:a006536. sourceExperimental — accuracy not yet measured
The section “TEC Abnormalities May Contribute to Tumor Progression” links abnormal tumor vessels to invasion and metastasis, and describes a hypothesis that vessel leakiness impairs chemotherapy delivery. The paper also discusses TEC involvement in angiogenesis, but it does not establish the stronger claim that TECs promote drug resistance; its account of impaired drug delivery is explicitly hypothetical. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The results indicated that secretion of tumor necrosis factor-alpha (TNFα) by macrophages can impair endothelial barrier as validated by a higher number and faster dynamics of TC-EC interactions in highly invasive fibrosarcoma cells [56].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Supportedcites [56] Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci. 2012;109:13515–20. source
The Results report that neutralizing soluble TNF-α in macrophage experiments reduced endothelial permeability, supporting a role for macrophage-secreted TNF-α in barrier impairment. In separate Results experiments with highly invasive HT1080 fibrosarcoma cells, TNF-α-stimulated endothelium had more tumor–endothelial interactions and faster tumor-cell passage across the barrier. (LLM, conf=0.89)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The combination of chemotherapeutic like α-cyano-4-hydroxycinnamate (CHC) alone and in combination with metformin is reported to hinder autophagic flux in CAFs and hampers tumor cell proliferation, irrespective of chemotherapeutic agents in in vitro and in syngeneic pancreatic cancer model [86].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Cancer-associated fibroblast (CAFs)
What the sources say
- Partly supportedcites [86] Zhang X, Schönrogge M, Eichberg J, Wendt EHU, Kumstel S, Stenzel J, Lindner T, Jaster R, Krause BJ, Vollmar BJFio. Blocking autophagy in cancer-associated fibroblasts supports chemotherapy of pancreatic cancer cells. Front Oncol. 2018;8:590. sourceExperimental — accuracy not yet measured
The ‘Chemotherapeutical Agents Modulate Autophagy’ section reports that CHC alone and with metformin blocked autophagic flux in CAFs, and the proliferation results show that both treatments inhibited pancreatic cancer-cell proliferation in vitro. The Discussion reports that blocking CAF autophagy inhibited proliferation with or without the tested drugs, but does not establish that CHC’s effect was independent of other agents. In the syngeneic model, CHC alone or with metformin produced only a minor decrease in tumor weight; the paper does not demonstrate the claimed CAF-flux and proliferation effects in vivo. Page numbers are unavailable in our copy. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CAFs residing in TME are heterogeneous cells with different origins, different functions (pro or anti-tumor activities) and different surface markers such as alpha-smooth muscle actin (α-SMA), myosin light chain 9 (MYL9), myosin light chain kinase (MYLK), matrix metalloproteinase 2 (MMP2), decorin (DCN) and collagen type I alpha 2 (COL1A2) [60–63].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Cancer-associated fibroblast (CAFs)
What the sources say
- Partly supportedcites [60] Liu T, Zhou L, Li D, Andl T, Zhang Y. Cancer-associated fibroblasts build and secure the tumor microenvironment. Front Cell Dev Biol. 2019;7:60. sourceExperimental — accuracy not yet measured
The HETEROGENEITY OF STROMAL FIBROBLASTS, MYOFIBROBLASTS, AND CAFs section describes CAFs as having different origins and functions, including tumor-supporting and tumor-suppressing activity. It reports α-SMA, MYLK, and MYL9 expression in tumor myofibroblasts, and MMP2, DCN, and COL1A2 in a CAF population. It does not describe all six as CAF surface markers; the cited findings distinguish myofibroblasts from CAFs. (LLM, conf=0.86)
- Partly supportedcites [61] Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E. In search of definitions: Cancer-associated fibroblasts and their markers. Int J Cancer. 2020;146:895–905. sourceExperimental — accuracy not yet measured
The Background describes CAFs as heterogeneous, and the Conclusion describes both tumor-promoting and tumor-suppressing roles. Figure 2 names α-SMA, MMP2, DCN and COL1A2 in connection with CAF subtypes. However, the Positive markers table explicitly says α-SMA is not a surface marker, and searches for MYL9 and MYLK found no passage identifying them as CAF markers. Page numbers were not available in our copy. (LLM, conf=0.88)
- Partly supportedcites [62] Nishishita R, Morohashi S, Seino H, Wu Y, Yoshizawa T, Haga T, Saito K, Hakamada K, Fukuda S, Kijima H. Expression of cancer-associated fibroblast markers in advanced colorectal cancer. Oncol Lett. 2018;15:6195–202. sourceExperimental — accuracy not yet measured
The Introduction identifies α-SMA as a CAF marker, and the Discussion reports varying CAF-marker expression in advanced colorectal cancer. The paper does not establish different CAF origins or both pro- and anti-tumor activities, and it does not identify MYL9, MYLK, MMP2, DCN, or COL1A2 as CAF markers; it studies collagen I rather than COL1A2 specifically. (LLM, conf=0.88)
- Partly supportedcites [63] Brunel A, Samain R, Neuzillet C. Bousquet CJTCR: identification of two cancer-associated fibroblast markers revealing stromal heterogeneity in sustaining cancer progression and chemoresistance. Trans Cancer Res. 2018:S718–21. sourceExperimental — accuracy not yet measured
The editorial (pp. S718–S721) describes heterogeneous CAF subsets with distinct functions and identifies α-SMA as a commonly described marker. It says anti-tumor CAF functions are suspected but remain unproven; it does not establish different CAF origins or identify MYL9, MYLK, MMP2, DCN, or COL1A2 as CAF markers. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CAFs produce ECM proteins, which prompts immunosuppression of tumor cells by recruiting immunosuppressive cells [64, 65] such as monocytes and inducing immunosuppressive PD-1+ TAMs, as recently shown in breast cancer cells in vitro [66].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Cancer-associated fibroblast (CAFs)
What the sources say
- Partly supportedcites [64] Monteran L, Erez N. The dark side of fibroblasts: Cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment. Front Immunol. 2019;10:1835. sourceExperimental — accuracy not yet measured
The Tumor-Associated Macrophages section (page unavailable) reports that CAF-derived Chi3L1 promotes macrophage recruitment and differentiation toward an immunosuppressive M2-like phenotype in a mouse model of breast cancer. It does not identify those macrophages as PD-1+ TAMs or describe that breast-cancer finding as an in vitro experiment. The sentence cites other sources for the earlier recruitment claim; the unsupported details are in the clause attached to this citation. (LLM, conf=0.84)
- Partly supportedcites [65] Liu T, Han C, Wang S, Fang P, Ma Z, Xu L, Yin R. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J Hematol Oncol. 2019;12:86. sourceExperimental — accuracy not yet measured
The CAF-related anti-tumor immune response sections state that CAFs produce ECM components and can recruit monocytes and promote their differentiation into TAMs (pages unavailable in our copy). They do not report induction of PD-1+ TAMs in breast cancer cells in vitro; the cited review discusses TAM recruitment in other contexts. (LLM, conf=0.86)
- Supportedcites [66] Gok Yavuz B, Gunaydin G, Gedik ME, Kosemehmetoglu K, Karakoc D, Ozgur F, Guc D. Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1+ TAMs. Sci Rep. 2019;9:3172. source
The citation to this paper is attached to the claim about monocyte recruitment and immunosuppressive PD-1+ TAMs, not the preceding ECM-protein claim. The Discussion (page unavailable) reports that CAFs recruit monocytes and differentiate them into immunosuppressive M2-like macrophages; it describes the study as using breast-cancer samples and in vitro cell lines. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In this report, activation of IL1/leukemia inhibitory factor (LIF)/janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling generate inflammatory CAFs while TGFβ signaling antagonizes this process by downregulating interleukin 1 receptor, type I (IL1R1) expression and promoting differentiation into myofibroblasts [73].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Cancer-associated fibroblast (CAFs)
What the sources say
- Supportedcites [73] Biffi G, Oni TE, Spielman B, Hao Y, Elyada E, Park Y, Preall J, Tuveson DA. IL-1-induced JAK/STAT signaling is antagonized by TGF-beta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 2018:9:282–301. source
The Results section states that tumor-secreted IL-1 activates an autocrine LIF/JAK/STAT cascade that maintains the inflammatory CAF phenotype (Figure 7J). It also states that TGF-β downregulates IL-1R1, prevents that cascade, and shifts CAFs toward a myofibroblastic state (Figures 7J and 5H). (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It has been recognized that TAMs may have both promoting (M1 type) and impairing roles (M2 type) when interfering with cancer treatments [92].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor-associated macrophage
What the sources say
- Partly supportedcites [92] Cassetta L, Kitamura T. Targeting tumor-associated macrophages as a potential strategy to enhance the response to immune checkpoint inhibitors. Front Cell Developmental Biol. 2018;6:38. sourceExperimental — accuracy not yet measured
The section ‘Targeting TAM Potentiates the Efficacy of Checkpoint Inhibitors’ identifies an M2 macrophage population as immunosuppressive and describes how shifting TAMs toward immune-activating functions can improve checkpoint therapy. The Conclusion and Future Perspectives likewise contrasts immunosuppressive with tumoricidal macrophages. The paper does not identify the treatment-promoting macrophages as ‘M1 type,’ so that specific classification is not established by our copy. (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Surprisingly, when interacting with apoptotic cancer cells in conditioned medium, TAMs inhibits TGFβ1-induced EMT and thus tumor invasion, which is considered the antitumor role of TAMs [95].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor-associated macrophage
What the sources say
- Supportedcites [95] Kim Y-B, Ahn Y-H, Jung J-H, Lee Y-J, Lee J-H, Kang JL. Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis. Cell Mol Immunol. 2019;16:851–67. source
The Results section reports that conditioned medium from macrophages exposed to apoptotic cancer cells inhibited TGF-β1-induced EMT. The Discussion says that TAMs in contact with apoptotic cancer cells can play an antitumor role by inhibiting EMT, migration, and invasion. The wording about interaction 'in conditioned medium' is imprecise, but the attributed finding is supported. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“It could be shown that TAM influences the migration rate of cancer cells by TGFβ1-induced MT1-MMP and the cancer cell migration persistence by the nuclear factor Kappa - light chain enhancer of activated B cells (NF-κB)-dependent MMP1 expression.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor-associated macrophage
What the sources say
- Supportedcites [110] Li R, Hebert JD, Lee TA, Xing H, Boussommier-Calleja A, Hynes RO, Lauffenburger DA, Kamm RD. Macrophage-secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways. Cancer Res. 2017;77:279–20. source
The Discussion states that macrophage-released TGFβ1 increases cancer-cell migration speed through MT1-MMP expression. It also describes a TNFα- and TGFβ1-driven NF-κB pathway that increases MMP1 expression and migration persistence. (LLM, conf=0.93)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ECM forms the scaffold of tissues and organs through the production of supramolecular aggregates, such as fibrils and sheet-like networks [113, 114].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Not checked — no full text of the sourcecites [113] Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123:4195–200. source
- Partly supportedcites [114] Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326:1216–9. sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says ECM provides structural support for organs and tissues and forms basement membranes beneath cell layers. The paper also discusses fibrils, but the passages in our copy do not describe ECM producing supramolecular aggregates or specify sheet-like networks as the means of support. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ECM may act as a barrier for drug delivery through increased tissue stiffness and desmoplasia or a gate for breaching the basement membrane to promote metastasis [2, 122].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Not checked — no full text of the sourcecites [2] Jahanban-Esfahlan R, Seidi K, Banimohamad-Shotorbani B, Jahanban-Esfahlan A, Yousefi B. Combination of nanotechnology with vascular targeting agents for effective cancer therapy. J Cell Physiol. 2017;233:2982–92. source
- Partly supportedcites [122] Jabłońska-Trypuć A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhibition Med Chem. 2016;31:177–83. sourceExperimental — accuracy not yet measured
The sections on MMPs and cancer and on invasion and metastasis describe ECM barriers being broken down and ECM degradation facilitating cancer-cell migration and metastasis (page unavailable). The paper does not say that stiffness or desmoplasia makes the ECM a barrier to drug delivery. Its explicit discussion of basement-membrane disruption is about angiogenesis, not metastatic breaching. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, hypoxia, which is common in collagen-rich tumors, promotes cancer progression [124].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Supportedcites [124] Xu S, Xu H, Wang W, Li S, Li H, Li T, Zhang W, Yu X, Liu L. The role of collagen in cancer: from bench to bedside. J Transl Med. 2019;17:309. source
The section “The reciprocity between collagen and cancer cells under hypoxic conditions” states that hypoxia is common in collagen-rich extracellular matrix and intensifies cancer progression. This directly supports the citing sentence. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the case of intravenous injection, the antibody-drug conjugate was found to bind to tenascin-C and the drug was discharged when the protease-sensitive linker between the antibody and the drug was cleaved.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Partly supportedcites [135] Dal Corso A, Gébleux R, Murer P, Soltermann A, Neri D. A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo. J Control Release. 2017;264:211–8. sourceExperimental — accuracy not yet measured
The Abstract identifies F16 as binding the A1 domain of tenascin-C, and the Therapy experiments section reports intravenous administration of F16-PNU159682 to mice (page numbers unavailable). The Abstract describes a protease-cleavable linker, but the Discussion calls extracellular protease cleavage in the tumor a conceivable mechanism rather than an established observation after injection. The claim overstates that part as a finding. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“It also derive proliferation, angiogenesis and metastasis stages of tumor progression [134].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Supportedcites [134] Lowy CM, Oskarsson T. Tenascin C in metastasis: a view from the invasive front. Cell Adhes Migr. 2015;9:112–24. source
The ‘Diverse cellular roles in metastatic progression’ section states that tenascin-C is associated with increased cancer-cell proliferation, promotes tumor angiogenesis, and supports metastatic growth. Its discussion of proliferation and angiogenesis further substantiates those roles. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Also, bi-transgenic tumor model confirmed the role of stromal collagen condensation as indication for mammary tumor initiation and progression.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Partly supportedcites [129] Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 2006;4:38. sourceExperimental — accuracy not yet measured
The Results section (‘Tumor-associated collagen signatures’; page unavailable) reports that dense collagen near a tumor was a reliable hallmark for locating small, pre-palpable tumors. It does not establish that collagen condensation indicates tumor initiation or progression: the authors explicitly say it is unclear whether the dense region precedes tumor formation. The Methods describe two mouse tumor models, not a bi-transgenic model that confirmed the claimed role. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other ECM components with therapeutic value include fibronectin extra domain A and B (anti-EDB aptide) [138], laminin (IKVAV) [139], gelatin (anginex, small geletic-1 binding peptide) [140], aggrecan (a conjugate of quaternary ammonium) [141], and heparan sulfate (CGKRK peptide), among others [142].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Not checked — no full text of the sourcecites [138] Park J, Kim S, Saw PE, Lee IH, Yu MK, Kim M, Lee K, Kim YC, Jeong YY, Jon S. Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging. J Control Release. 2012;163:111–8. source
- Not checked — no full text of the sourcecites [139] Okur AC, Erkoc P, Kizilel S. Targeting cancer cells via tumor-homing peptide CREKA functional PEG nanoparticles. Colloids Surf B Biointerfaces. 2016;147:191–200. source
- Partly supportedcites [140] Upreti M, Jyoti A, Johnson SE, Swindell EP, Napier D, Sethi P, Chan R, Feddock JM, Weiss HL, O'Halloran TV, Evers BM. Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer. Oncotarget. 2016;7:41559–74. sourceExperimental — accuracy not yet measured
The Research Paper section describes anginex as a galectin-1-binding peptide and a ligand for targeted delivery to tumor endothelium, supporting the anginex portion attached to citation [140]. It does not identify gelatin as the target or establish anginex as a gelatin-targeting therapy. No page number is available in our copy. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“This formulation allowed drug targets to bind to the tumor stroma to exert their effects locally and gained a promising efficacy and safety profile compared to the unconjugated molecules tested in several mouse models.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Supportedcites [137] Ishihara J, Ishihara A, Sasaki K, Lee SS-Y, Williford J-M, Yasui M, Abe H, Potin L, Hosseinchi P, Fukunaga K, et al. Targeted antibody and cytokine cancer immunotherapies through collagen affinity. Sci Transl Med. 2019;11:eaau3259. source
The Abstract reports that the collagen-binding formulation targets exposed tumor-stroma collagen and that the modified drugs reduced toxicity and suppressed tumor growth compared with unmodified drugs in multiple murine cancer models. The Discussion describes the tumor stroma matrix as both a drug target and a drug reservoir. Page numbers are not provided in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Their results indicated that simultaneous administration of anti-CD274 antibody (also known as PD-L1 or B7-H1) and anti-CD47 checkpoints antibody can respectively block the signal of “don’t find me” for immune evasion and “don’t eat me” for phagocytosis on CTCs.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Supportedcites [153] Lian S, Xie R, Ye Y, Lu Y, Cheng Y, Xie X, Li S, Jia LJSr. Dual blockage of both PD-L1 and CD47 enhances immunotherapy against circulating tumor cells. Sci Rep. 2019;9:4532. source
The Abstract states that antibodies simultaneously block CD274 (PD-L1/B7-H1) and CD47 on CTCs, identifying them respectively as the “don’t find me” and “don’t eat me” signals. The Introduction gives the same signal assignments. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“They facilitate specific cell-cell interactions and stimulate several signaling pathways in their target cells, including cancer cells [173].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Supportedcites [173] Sullivan R, Maresh G, Zhang X, Salomon C, Hooper J, Margolin D, Li L. The emerging roles of extracellular vesicles as communication vehicles within the tumor microenvironment and beyond. Front Endocrinol (Lausanne). 2017;8:194. source
The figure caption in “Communication via EVs within the TME” (page not supplied) describes bidirectional communication via exosomes between tumor cells and other cells, with cargo influencing multiple pathways involved in tumor progression. The “Proliferation” section also gives examples of vesicles affecting signaling and proliferation in recipient cancer cells. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, these combination shifts immune evasion to immune activation, which resulted in enhanced anti-tumor growth activity and reduced CTCs metastasis in 4 T1 tumor mouse model in vivo [153].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Supportedcites [153] Lian S, Xie R, Ye Y, Lu Y, Cheng Y, Xie X, Li S, Jia LJSr. Dual blockage of both PD-L1 and CD47 enhances immunotherapy against circulating tumor cells. Sci Rep. 2019;9:4532. source
The Results (Fig. 2F) depict dual CD47/PD-L1 blockade changing immune evasion to immune activation. The Abstract and Results report stronger inhibition of tumor growth and CTC metastasis in the in vivo 4T1 mouse model with dual blockade than with either antibody alone. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, dimeric 123B9 conjugation with paclitaxel is found to be very useful in combating CTCs and preventing the lung metastasis in breast cancer models [168].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Supportedcites [168] Salem AF, Wang S, Billet S, Chen J-F, Udompholkul P, Gambini L, Baggio C, Tseng H-R, Posadas EM, Bhowmick NA, Pellecchia M. Reduction of circulating Cancer cells and metastases in breast-Cancer models by a potent EphA2-agonistic peptide–drug conjugate. J Med Chem. 2018;61:2052–61. source
The Results section on circulating tumor cells reports significantly fewer CTCs after (123B9)2–L2–PTX treatment than after Abraxane in an orthotopic breast-cancer mouse model. The Results section on the breast-cancer metastasis model reports more than 75% fewer gross lung metastases than in the control and Abraxane groups. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, they can serve as valuable prognostic, diagnostic, and biosensing tools to detect cancer cells that are clinically undetectable, and to make plans for timely and precise therapeutic interventions (Fig. 2e) [9].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Partly supportedcites [9] Jahanban-Esfahlan R, Seidi K, Manjili MH, Jahanban-Esfahlan A, Javaheri T, Zare P. Tumor cell dormancy: threat or opportunity in the fight against Cancer. Cancers. 2019;11:1207. sourceExperimental — accuracy not yet measured
The Introduction identifies CTCs as detectable dormant tumor cells, and the Conclusions and Clinical Implications say that CTCs and other circulating material offer opportunities for timely detection and monitoring of treatment outcomes. The paper does not establish CTCs specifically as prognostic or biosensing tools for planning precise interventions; it cautions that their rarity makes minimal residual disease difficult to detect. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the development of liquid biopsy platforms capable of capturing this rare population of cells from the blood is highly rewarding [155].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Supportedcites [155] Jahanban-Esfahlan R, Seidi K, Jahanban-Esfahlan A, Jaymand M, Alizadeh E, Majdi H, Najjar R, Javaheri T, Zare P. Static DNA nanostructures for cancer theranostics: Recent progress in design and applications. Nannotechnol Sci Appl. 2019;12:25–46. source
The DNA Hydrogel section describes a liquid-biopsy method that captures circulating tumor cells and calls it an effective tool for live single-cell isolation. The Introduction identifies detection and analysis of rare circulating tumor cells as a use in predictive cancer diagnostics. Together, these passages support the claim that developing platforms to capture these cells is valuable. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Consequently, tumor self-seeding leads to enhanced angiogenesis, tumor growth, stromal recruitment through seed-derived factors including the chemokine CXCL1, anaplasia, tumor size, and vascularity.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Partly supportedcites [147] Kim M-Y, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH-F, Norton L, Massagué J. Tumor self-seeding by circulating cancer cells. Cell. 2009;139:1315–26. sourceExperimental — accuracy not yet measured
The Abstract and Discussion report that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment; the Results identify seeder-derived CXCL1 as contributing to stromal recruitment. But the Discussion presents links to anaplasia, tumor size, and vascularity as possible explanations for clinical associations, not as established outcomes of self-seeding. Page numbers are not provided in our copy. (LLM, conf=0.88)
- Partly supportedcites [148] Jayatilaka H, Phillip JM. Targeting metastasis through the inhibition of interleukin 6 and 8. Future Medicine. 2019. https://doi.org/10.2217/bmt-2019-0002. sourceExperimental — accuracy not yet measured
The Abstract reports that IL-6 and IL-8 promote tumor self-seeding and co-regulate tumor-cell proliferation; it also mentions interactions with stromal cells. It does not say that self-seeding causes the listed changes in angiogenesis, stromal recruitment, anaplasia, tumor size, or vascularity, or identify CXCL1 as a seed-derived factor. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Another study, involving 6712 breast cancer patients showed a decrease in the number of CTCs only in human epidermal growth factor receptor 2 (HER2+) or HER2- patients but not in the triple-negative ones and nor in patients who underwent surgery.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Partly supportedcites [151] Yan W-T, Cui X, Chen Q, Li Y-F, Cui Y-H, Wang Y, Jiang JJSr. Circulating tumor cell status monitors the treatment responses in breast cancer patients: a meta-analysis . Sci Rep. 2017;7:43464. sourceExperimental — accuracy not yet measured
The Results describe a meta-analysis of 50 studies involving 6,712 patients. Subgroup analyses report significant decreases in CTC-positive rates for HER2-positive and HER2-negative patients, but not for triple-negative patients or after surgery. The claim calls these decreases changes in the number of CTCs, whereas the paper distinguishes CTC-positive rates from CTC counts; its initial pooled count analysis found no significant change. Page numbers were not supplied. (LLM, conf=0.89)
plainn = 6,712- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, these exosomes display differential integrin expression, and blockade of integrins αvβ5 and α6β4 dampen exosome uptake, as well as liver and lung metastasis, respectively.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Supportedcites [176] Hoshino A, Costa-Silva B, Shen T-L, Rodrigues G, Hashimoto A, Mark MT, Molina H, Kohsaka S, Di Giannatale A, Ceder SJN: Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35. source
The Abstract reports distinct exosomal integrin patterns and states that targeting α6β4 and αvβ5 decreased exosome uptake and lung and liver metastasis, respectively. The cited claim gives the same organ associations in reverse order: αvβ5 with liver and α6β4 with lung. The sections “Exosomal ITGs determine organotropism” and “Exosomal tropism requires ITGβ4 and ITGβ5” provide supporting experimental detail. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Finally, integrin-mediated uptake of exosome activates Src phosphorylation and pro-inflammatory S100 gene expression in resident cells [176].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Supportedcites [176] Hoshino A, Costa-Silva B, Shen T-L, Rodrigues G, Hashimoto A, Mark MT, Molina H, Kohsaka S, Di Giannatale A, Ceder SJN: Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35. source
In “Exosomal ITGs activate S100 genes” (page not supplied), the paper reports an exosomal integrin-dependent increase in phosphorylated Src in lung fibroblasts and upregulation of pro-inflammatory S100 genes in target cells. The Discussion links cell-type-specific exosome integrin uptake to S100 gene upregulation, while noting that the response varies by resident cell type. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In this space, tumor cells and their adjacent microenvironments are in frequent communication.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Mechanism of interaction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The interaction of cancer cells with their microenvironment is dynamic and bidirectional and includes (i) cell-cell contacts, or cell-free contacts (involving ECM) and (ii) the mediators that enable these contacts.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Mechanism of interaction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The consequence of such crosstalks is reflected in tumor formation and maintenance as well as deficient response to therapy and multi-drug resistance (MDR).”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Background
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Tumors develop in complex and dynamic microenvironments that influencetheir growth, invasion, and metastasis.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Mechanism of interaction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the meantime, the detection and monitoring of other tumor-interacting components, such as CTCs, cfDNA and apoptotic bodies in the bloodstream can be beneficial to extend the knowledge of the condition of the malignant disease and improve cancer detection and diagnosis, as well as enable timely and appropriate treatment (Fig. 2).”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In fact, inhibitors of these pathways can target and block proliferation and pathological angiogenesis in vivo [53].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
What the sources say
- Not checked — no full text of the sourcecites [53] Missiaen R, Morales-Rodriguez F, Eelen G, Carmeliet P. Targeting endothelial metabolism for anti-angiogenesis therapy: a pharmacological perspective. Vasc Pharmacol. 2017;90:8–18. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Equally, 3D systems enable studying the organ-specific preference of metastatic cancer cells and the underlying molecular pathways/interactions.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Tumor endothelial cells (TECs)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, pericytes have several functions in the immune system including the attraction of inborn leukocytes to exit blood vessels, regulating lymphocyte activation and eliciting direct phagocytic activity [26].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Pericytes
What the sources say
- Not checked — no full text of the sourcecites [26] Birbrair A: Pericyte biology: development, homeostasis, and disease. In Pericyte Biology-Novel Concepts Springer; 2018: 1–3. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Such liposomes were capable of regulating the tumor ECM through efficiently removing CAFs, rendering the ECM accessible for doxorubicin-loaded nanoparticles that were administered later [136].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > ECM
What the sources say
- Not checked — no full text of the sourcecites [136] Chen B, Dai W, Mei D, Liu T, Li S, He B, He B, Yuan L, Zhang H, Wang X. Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system. J Control Release. 2016;241:68–80. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This aptamer-conjugate can work properly when 108 interfering cells or blood cells that do not express EpCAM or Her2 are present, as well as in complex biological samples of patients and mice with greatly enhanced bio-stability and high capturing precision.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Not checked — no full text of the sourcecites [154] Dong H, Han L, Wu Z-S, Zhang T, Xie J, Ma J, Wang J, Li T, Gao Y, Shao J. Biostable aptamer rings conjugated for targeting two biomarkers on circulating tumor cells in vivo with great precision. Chem Mater. 2017;29:10312–25. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this line, an interesting formulation based on DNA hydrogel is developed in which a DNA staple strand with aptamer-toehold biblocks binds to EpCAM receptor. This CTC-specific binding, initiate aptamer-triggered clamped hybridization chain reaction via toehold-initiated branch migration on CTC surface, realizing single/clusters of live CTC clocked in DNA hydrogel.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Not checked — no full text of the sourcecites [156] Song P, Ye D, Zuo X, Li J, Wang J, Liu H, Hwang MT, Chao J, Su S, Wang L, et al. DNA hydrogel with Aptamer-toehold-based recognition, cloaking, and Decloaking of circulating tumor cells for live cell analysis. Nano Lett. 2017;17:5193–8. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, despite uncertainty about the analytic validity, clinical validity, and clinical utility of CTCs, their status is a valuable indicator of the efficacy of cancer therapy, which may aid clinicians to make decisions for further personalized therapy.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this formulation, capture arms could distinctly bind two biomarkers at the same time (EpCAM and Her2). This, induced apoptosis as a result of the arrestment of cell cycle and the inhibition of tumor progression in captured CTCs (Fig. 3) [154].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Not checked — no full text of the sourcecites [154] Dong H, Han L, Wu Z-S, Zhang T, Xie J, Ma J, Wang J, Li T, Gao Y, Shao J. Biostable aptamer rings conjugated for targeting two biomarkers on circulating tumor cells in vivo with great precision. Chem Mater. 2017;29:10312–25. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The aptamer-conjugate impeded metastasis and displayed enhanced bio-stability against endogenous nucleases in vivo.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Circulating tumor cells
What the sources say
- Not checked — no full text of the sourcecites [154] Dong H, Han L, Wu Z-S, Zhang T, Xie J, Ma J, Wang J, Li T, Gao Y, Shao J. Biostable aptamer rings conjugated for targeting two biomarkers on circulating tumor cells in vivo with great precision. Chem Mater. 2017;29:10312–25. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Form therapeutic point of view, exosomes are applied as diagnostic biomarkers, therapeutic targets, or as anticancer drug-delivery vehicles [178].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Not checked — no full text of the sourcecites [178] Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell. 2016;30:836–48. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, Nishida-Aoki and colleagues applied therapeutic antibody targeting EVs including human-specific anti-CD9 or anti-CD63 antibodies which aimed at decreasing tumor-derived exosomes generation, possibly through clearance of EVs by macrophages, resulting in a decline in breast cancer distant metastasis in a mouse model (Fig. 2f) [186].”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
What the sources say
- Not checked — no full text of the sourcecites [186] Nishida-Aoki N, Tominaga N, Takeshita F, Sonoda H, Yoshioka Y, Ochiya T. Disruption of circulating extracellular vesicles as a novel therapeutic strategy against cancer metastasis. Mol Ther. 2017;25:181–91. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Findings from preclinical animal models are predictive of therapeutic outcomes in human cancer patients.
“This formulation is found as a promising approach in treatment of a variety of cancers including breast, lung, colon and melanoma in preclinical settings [92].”
The paper relies on this without support.
In vitro 3D and microfluidic models sufficiently recapitulate the in vivo tumor microenvironment to inform therapeutic development.
“Recent advances on three dimensional (3D) platforms through the use of lab-on-chip and microfluidic devices [17] have provided an enormous opportunity to better stimulate the function and biology of TME and to bridge the translational gap between preclinical and clinical settings [18].”
The authors state this as an assumption.
Disrupting tumor cell interactions can be exploited as a novel strategy for future cancer therapy regimes.
“Together, we assume that disrupting tumor cell interactions can be exploited as a novel strategy for future cancer therapy regimes; however, further studies are still pending for clinical implementation in order to fully understand tumor cell interactions.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“With the advancement of tumor biology, it became clear that tumor cells actively reprogram surrounding fibroblasts into a modified state termed cancer-associated fibroblasts (CAFs) [5,19,35,36].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This biochemical framework imparts key biophysical properties to the tumor tissue, including stiffness, porosity, insolubility, and molecular density [5,77,78,79]. These characteristics serve as biomechanical cues that modulate diverse cellular processes, such as migration, proliferation, polarity maintenance, and lineage specification [25,80].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The dynamic interactions between tumor cells and the non-transformed cells are key in determining the progression of cancer, as these could either suppress or promote cancer initiation, growth, migration, and metastasis, as well as cancer recurrence and drug resistance (2)”
From Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis (2021) · cites this paper as [2]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“It is now widely accepted that tumor initiation and progression are not governed solely by genetic mutations but are significantly influenced by the dynamic interplay between tumor cells and their surrounding microenvironment.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“This surrounding landscape—referred to as the tumor microenvironment (TME)—comprises a complex network of cellular, acellular, and immune components [5,20,21].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [5]
In the citing paper
“Single‐cell‐based technologies have enabled a better dissection of the TME through precise monitoring of cell sub‐populations and spatial architecture, thus revealing the heterogeneous and complex nature of the TME [10, 12].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
“To increase nutrient availability, breast cancer cells secrete miR-122 -enriched vesicles to suppress glucose uptake by niche cells in vitro and in vivo.”
§ Tumor microenvironment complexity and therapeutic implications at a glance > Understanding tumor cell interactions for effective cancer theranostics > Exosomes
“Mechanistically, miR-122 downregulate the glycolytic enzyme pyruvate kinase and restores glucose uptake by lungs and brain and lessen disease progression [177].”
Citations
Cites
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994 · cited 1×
“In view of the critical role of CAFs in the design of TME, the therapeutic options for deactivating CAF-mediated interaction are largely focused on using/reprogramming or eliminating of CAFs [76] [77] [78] .”
BackgroundThe chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · cited 1×
“Based on their origin and half-life, they are (i) long-living embryonically (yolk sac)-derived tissue-resident macrophages and (ii) short-lived circulating monocyte-derived macrophages derived from bone marrow and recruited to tumor tissue by growth factors and chemokines, such as, CCL2, CCL5, and macrophage colony-st…”
BackgroundTumour exosome integrins determine organotropic metastasis
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., Di Giannatale, A., Ceder, S., et al. (2015) · Nature · doi:10.1038/nature15756 · Cited by 5,101 · cited 1×
“Finally, integrin-mediated uptake of exosome activates Src phosphorylation and pro-inflammatory S100 gene expression in resident cells [176].”
BackgroundAccessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632 · cited 1×
“The non-malignant cells in the TME are known to promote tumorigenesis in all phases of cancer development and metastasis [4, 5] .”
BackgroundThe biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366 · cited 1×
“apoptosis and improving the proliferation, migration and viability of cancer cells [58, 59].”
BackgroundThe extracellular matrix at a glance
Frantz, C., Stewart, K. M., & Weaver, V. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.023820 · Cited by 4,334 · cited 1×
“ECM forms the scaffold of tissues and organs through the production of supramolecular aggregates, such as fibrils and sheet-like networks [113, 114] .”
BackgroundTumour-associated macrophages as treatment targets in oncology
Mantovani, A., Marchesi, F., Malesci, A., Laghi, L., & Allavena, P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.217 · Cited by 4,157 · cited 1×
“TAM targeting, in turn, can be achieved by barricading the colony stimulating factor 1 receptor (CSF1R), which is essential for the recruitment, differentiation and survival of TAM [103] (Fig.”
BackgroundTumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089 · cited 2×
“Accordingly, TAM-based therapeutic strategies are being developed that aim at TAM targeting, TAM reeducation, and TAM depletion [88, 96, 101, 102] .”
BackgroundThe Extracellular Matrix: Not Just Pretty Fibrils
Hynes, R. O. (2009) · Science · doi:10.1126/science.1176009 · Cited by 3,527 · cited 1×
“ECM forms the scaffold of tissues and organs through the production of supramolecular aggregates, such as fibrils and sheet-like networks [113, 114] .”
BackgroundTumour-cell invasion and migration: diversity and escape mechanisms
Friedl, P., & Wolf, K. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1075 · Cited by 3,350 · cited 1×
“And most of them only discussed a limited number of players/strategies such as anti-angiogenic therapies or targeting ECM yet fail to discuss the newly formed gadgets of cell-cell interactions such as cfDNA, apoptotic bodies, CTCs as well as exosomes [21, 22] .”
Background
Cited by
Sorted by citations
Items 201–300 of 1,790
Gharib, E., & Robichaud, G. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179463 · Cited by 55
Wang, L., Gu, M., Zhang, X., Kong, T., Liao, J., Zhang, D., & Li, J. (2025) · Advanced Science · doi:10.1002/advs.202413367 · Cited by 47
Sapudom, J., Müller, C. D., Nguyen, K.-T., Martin, S., Anderegg, U., & Pompe, W. (2020) · Gels · doi:10.3390/gels6040033 · Cited by 49
Zhang, J., Wang, Z., Zhang, X., Dai, Z., Zhi-peng, W., Yu, J., Peng, Y., Wu, W., Zhang, N., Luo, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.810471 · Cited by 44
“Tumor microenvironment (TME) is a complex and dynamic environment around tumor consisting of surrounding immune cells, signaling molecules, blood vessels, and the extracellular matrix (ECM) (7, 8).”
BackgroundMetallic Nanoparticle-Mediated Immune Cell Regulation and Advanced Cancer Immunotherapy
Mohapatra, A., Padmanaban, S., & Park, I. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111867 · Cited by 46
“In short, increased ROS generation leads to the secretion of IL-1β, IL-8, IL-6, CXCL-12, TNF, NOX2, COX-2 and IL-2 (Figure 4) into the ECM of the tumor, suggesting that ROS stimulates the multiplication of tumor cells and downregula- Pharmaceutics 2021, 13, 1867 9 of 28 tion of all apoptotic factors, thus promoting tu…”
BackgroundInfluentialShahpouri, M., Adili-Aghdam, M. A., Mahmudi, H., Jaymand, M., Amoozgar, Z., Akbari, M., Hamblin, M. R., & Jahanban‐Esfahlan, R. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.12.009 · Cited by 45
Self-citationFang, T., Cao, X., Wang, L., Chen, M., Deng, Y., & Chen, G. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.10.023 · Cited by 44
Imodoye, S. O., Adedokun, K. A., & Bello, I. O. (2024) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02258-6 · Cited by 47
“…density, the ECM is vulnerable to remodeling in terms of stiffness and enzymatic degradation, especially under the influence of tumor stromal and cancer cells, which promote cancer cell proliferation, migration, invasion, angiogenesis, and immune evasions (Belli et al. 2018; Baghban et al. 2020).”
Aramini, B., Masciale, V., Arienti, C., Dominici, M., Stella, F., Martinelli, G., & Fabbri, F. (2022) · Cancers · doi:10.3390/cancers14102408 · Cited by 42
“In particular, the tumor microenvironment (TME) and the interactions between cancer cells and non-cancer cells are crucial for cancer progression [110,111].”
BackgroundBridges, K., & Miller‐Jensen, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.885267 · Cited by 48
“signals, and extracellular matrix (5, 6).”
Fisher, T. B., Saini, G., Rekha, T. S., Krishnamurthy, J., Bhattarai, S., Callagy, G., Webber, M., Janssen, E. A. M., Kong, J., & Aneja, R. (2024) · Breast Cancer Research · doi:10.1186/s13058-023-01752-y · Cited by 42
“Communication between TME components and their spatial relationships affect cancer progression, treatment response, and disease outcomes [12, 13].”
BackgroundNegrini, N. C., Ricci, C., Bongiorni, F., Trombi, L., D’Alessandro, D., Danti, S., & Farè, S. (2022) · Cancers · doi:10.3390/cancers14082003 · Cited by 42
“Our scaffolds had Young’s modulus values in the order of MPa, which are superior [16,48], or comparable [49,50] to those described in literature able to mimic metastatic and primary bone tumors.”
ResultNetwork-based integration of multi-omics data for clinical outcome prediction in neuroblastoma
Wang, C., Lue, W., Kaalia, R., Kumar, P., & Rajapakse, J. C. (2022) · Scientific Reports · doi:10.1038/s41598-022-19019-5 · Cited by 42
Mahmudi, H., Adili-Aghdam, M. A., Shahpouri, M., Jaymand, M., Amoozgar, Z., & Jahanban‐Esfahlan, R. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1054029 · Cited by 42
Self-citationGelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling
de Barros, N. R., Gomez, A., Ermis, M., Falcone, N., Haghniaz, R., Young, P., Gao, Y., Aquino, A.-F., Li, S., Niu, S., et al. (2023) · Biofabrication · doi:10.1088/1758-5090/ace0db · Cited by 46
SpaRx: elucidate single-cell spatial heterogeneity of drug responses for personalized treatment
Tang, Z., Liu, X., Li, Z., Zhang, T., Yang, B., Su, J., & Song, Q. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad338 · Cited by 46
“The spatial heterogeneity in cells and their microenvironment play critical roles in the treatment of complex diseases such as cancers [35] and AD [36].”
BackgroundPeptide-nanoparticle conjugates as a theranostic platform
Kim, S., No, Y. H., Sluyter, R., Konstantinov, K., Kim, J. H., & Kim, J. H. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215530 · Cited by 46
Metabolomics at the tumor microenvironment interface: Decoding cellular conversations
Berrell, N., Sadeghirad, H., Blick, T., Bidgood, C. L., Leggatt, G. R., O'Byrne, K. J., & Kulasinghe, A. (2023) · Medicinal Research Reviews · doi:10.1002/med.22010 · Cited by 44
Zhang, Z., Wiencke, J. K., Kelsey, K. T., Koestler, D. C., Christensen, B. C., & Salas, L. A. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03736-6 · Cited by 38
“The dynamic interactions between tumor cells and other cells in their microenvironment can promote tumor progression [3].”
BackgroundAssessment of spatial transcriptomics for oncology discovery
Lyubetskaya, A., Rabe, B. A., Fisher, A., Lewin, A. C., Neuhaus, I., Brett, C., Brett, T., Pereira, E. R., Golhar, R., Kebede, S., et al. (2022) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100340 · Cited by 42
Lipid peroxidation of immune cells in cancer
Xiao, L., Xian, M., Zhang, C., Guo, Q., & Yi, Q. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1322746 · Cited by 47
Li, F., Guo, H., Wang, Y., Liu, B., & Zhou, H. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106641 · Cited by 41
Khesht, A. M. S., Karpisheh, V., Gilan, P. S., Melnikova, L. A., Zekiy, A. O., Mohammadi, M., Hojjat‐Farsangi, M., Zolbanin, N. M., Mahmoodpoor, A., Hassannia, H., et al. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.07.034 · Cited by 40
RetractedFocal adhesion kinase inhibitors in the treatment of solid tumors: Preclinical and clinical evidence
Quispe, P. A., Lavecchia, M. J., & León, I. E. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.11.025 · Cited by 40
The use of machine learning to discover regulatory networks controlling biological systems
Erbe, R., Gore, J., Gemmill, K., Gaykalova, D. A., & Fertig, E. J. (2022) · Molecular Cell · doi:10.1016/j.molcel.2021.12.011 · Cited by 44
Lin, J., Li, D., Li, C., Zhuang, Z., Chu, C., Ostrikov, K., Thompson, E. W., Liu, G., & Wang, P. (2023) · Nanoscale · doi:10.1039/d3nr01735d · Cited by 43
On-chip recapitulation of the tumor microenvironment: A decade of progress
Giannitelli, S. M., Peluzzi, V., Raniolo, S., Roscilli, G., Trombetta, M., Mozetic, P., & Rainer, A. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122482 · Cited by 42
Two-dimensional nano-biomaterials in regulating the tumor microenvironment for immunotherapy
Xu, G., Li, J., Zhang, S., Cai, J., Deng, X., Wang, Y., & Pei, P. (2024) · Nano TransMed · doi:10.1016/j.ntm.2024.100045 · Cited by 40
Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy
Tang, Z., Deng, L., Zhang, J., Jiang, T., Xiang, H., Chen, Y., Liu, H., Cai, Z., Cui, W., & Xiong, Y. (2024) · Research · doi:10.34133/research.0477 · Cited by 46
de León, U. A.-P., Vázquez-Jiménez, A., Matadamas-Guzman, M. L., Pelayo, R., & Reséndis-Antonio, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.642842 · Cited by 43
“This type of modeling scheme may help develop therapeutic strategies to ensure stability despite the microenvironment acting against the treatment of a specific cancer type (37, 38).”
BackgroundGenetic Modifications That Expand Oncolytic Virus Potency
Cristi, F., Gutiérrez, T., Hitt, M., & Shmulevitz, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.831091 · Cited by 42
“The spaces between the cells are composed of interstitial fluid, cell-free DNA, exosomes, as well as ECM (Baghban et al., 2020).”
BackgroundZhang, Y., Yang, C., Sheng, R., Dai, Y., & Zeng, M. (2023) · La radiologia medica · doi:10.1007/s11547-023-01695-6 · Cited by 41
“…evaluation since changes in the tumor microenvironment often pre-cede signaling pathways that mediate tumor invasion[22, 23]; secondly, dynamic changes in tumor composition are closely related to tumor progression [24, 25], making quantitative metrics related to tumor composition-sensitive markers.”
BackgroundTumor microenvironment diversity and plasticity in cancer multidrug resistance
Li, Z., & Yin, P. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188997 · Cited by 44
Paun, R. A., Jurchuk, S., & Tabrizian, M. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10601 · Cited by 48
“8,9 13 – 15 Furthermore, the aberrant vascular and lymphatic systems in the TME underline yet another aspect that may contribute to therapeutic resistance.”
BackgroundSharma, R., & Malviya, R. (2024) · Medicine Advances · doi:10.1002/med4.51 · Cited by 40
Chen, M., Choi, H. K., Goldston, L. L., Hou, Y., Jiang, C., & Lee, K. (2025) · ACS Nano · doi:10.1021/acsnano.5c06940 · Cited by 43
Hong, Y., & Kim, I. (2022) · BMB Reports · doi:10.5483/bmbrep.2022.55.1.075 · Cited by 39
“ly induce positive responses in most patients, but is associated with frequent relapses and resistance (2, 3).”
BackgroundO-GlcNAcylation and Its Role in Cancer-Associated Inflammation
Ouyang, M., Yu, C., Deng, X., Zhang, Y., Zhang, X., & Duan, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.861559 · Cited by 43
Tan, K., & Naylor, M. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.876451 · Cited by 39
Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery
Jang, H., Kim, H., Kim, E. H., Han, G., Jang, Y., Kim, Y., Lee, J. W., Shin, S. C., Kim, E. E., Kim, S. H., et al. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00456-w · Cited by 43
“One such modification involves addressing the extracellular matrix, a prominent constituent of the TME, which acts as a physical barrier impeding drug delivery to cancer cells [49].”
BackgroundJiang, Y., Chao, C., Chang, A., Chen, P., Cheng, F., Liu, J., Liu, P., Huang, C., Guo, J., Huang, W., et al. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.12.011 · Cited by 38
“Cancer cells have been termed the ‘‘heart” of the TME, harnessing nonmalignant cells to work for the benefit of cancer cells, leading to tumor progression and distant metastasis [5].”
BackgroundCirculating Tumor Cells in Colorectal Cancer: Detection Systems and Clinical Utility
Petrik, J., Verbanac, D., Fabijanec, M., Hulina, A., Čeri, A., Bačura, A. S., Petlevski, R., Rajković, M. G., Rumora, L., Krušlin, B., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113582 · Cited by 40
“Tumor growth and its invasiveness depend on the malignant transformation of the cells that form the microenvironment and the patient’s immune response [15].”
BackgroundCa2+ Signalling and Hypoxia/Acidic Tumour Microenvironment Interplay in Tumour Progression
Audero, M. M., Prevarskaya, N. B., & Fiorio, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137377 · Cited by 40
Therapy-Induced Stromal Senescence Promoting Aggressiveness of Prostate and Ovarian Cancer
Pardella, E., Pranzini, E., Nesi, I., Parri, M., Spatafora, P., Torre, E., Muccilli, A., Castiglione, F., Fambrini, M., Sorbi, F., et al. (2022) · Cells · doi:10.3390/cells11244026 · Cited by 41
“establishing bidirectional and dynamic crosstalk with tumor cells [60,61].”
BackgroundThe Efficacy of Using Patient-Derived Organoids to Predict Treatment Response in Colorectal Cancer
Su, C., Olsen, K. A., Bond, C., & Whitehall, V. (2023) · Cancers · doi:10.3390/cancers15030805 · Cited by 37
“The tumour microenvironment includes stromal cancer-associated fibroblasts and immune cells, which may modulate response to therapy via the cross-talk of growth factors and cytokines [66].”
BackgroundClinical applications of graph neural networks in computational histopathology: A review
Meng, X., & Zou, T. (2023) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2023.107201 · Cited by 42
Immune cell networking in solid tumors: focus on macrophages and neutrophils
Ceglie, I. D., Carnevale, S., Rigatelli, A., Grieco, G., Molisso, P., & Jaillon, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1341390 · Cited by 38
The application of bacteria-nanomaterial hybrids in antitumor therapy
Xiao, S., Mu, M., Feng, C., Pan, S., & Chen, N. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02793-x · Cited by 41
Aggregation-induced emission-based fluorescent probes for cellular microenvironment detection
Li, X.-F., & Wu, F. (2025) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2025.117130 · Cited by 38
Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics
Serumula, W., Pillay, V., Hadebe, B., & Vorster, M. (2025) · Pharmaceuticals · doi:10.3390/ph18040522 · Cited by 38
“FAPI PET imaging provided crucial insights into complex infectious scenarios, aiding in accurate diagnosis [4].”
Oo, K. K., Kamolhan, T., Soni, A., Thongchot, S., Mitrpant, C., O-Charoenrat, P., Thuwajit, C., & Thuwajit, P. (2020) · BMC Cancer · doi:10.1186/s12885-020-07761-w · Cited by 39
Shueng, P., Yu, L.-Y., Chiu, H., Chang, H.-C., Chiu, Y., Kuo, T.-Y., Yen, Y.-W., & Lo, C.-L. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121012 · Cited by 37
Croft, P. K., Sharma, S., Godbole, N., Rice, G. E., & Salomón, C. (2021) · Cells · doi:10.3390/cells10092272 · Cited by 40
Multi-organ-on-chip approach in cancer research
Żuchowska, A., & Skorupska, S. (2021) · Organs-on-a-Chip · doi:10.1016/j.ooc.2021.100014 · Cited by 40
Modulating undruggable targets to overcome cancer therapy resistance
Passirani, C., Vessières, A., Regina, G. L., Link, W., & Silvestri, R. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100788 · Cited by 37
Baradaran, A., Asadzadeh, Z., Hemmat, N., Baghbanzadeh, A., Shadbad, M. A., Khosravi, N., Derakhshani, A., Alemohammad, H., Nour, M. A., Safarpour, H., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112588 · Cited by 37
RetractedNengroo, M. A., Verma, A., & Datta, D. B. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155916 · Cited by 39
Fisher, N. C., Byrne, R. M., Leslie, H., Wood, C. S., Legrini, A., Cameron, A. J., Ahmaderaghi, B., Corry, S. M., Malla, S. B., Amirkhah, R., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1102 · Cited by 36
“…when compared with the relative unpredictable nature of diagnostic sample acquisition, differences in the epithelial, immune, and stromal composition between the models and clinical samples (15) has the potential to confound our understanding and interpretationofthesesignaturesinspeci fi cdomains.”
Metabolic Reprogramming in Tumor-Associated Macrophages in the Ovarian Tumor Microenvironment
Kumar, S., Mittal, S., Gupta, P., Singh, M., Chaluvally–Raghavan, P., & Pradeep, S. (2022) · Cancers · doi:10.3390/cancers14215224 · Cited by 38
Self-assembling peptides as immunomodulatory biomaterials
Hernández, A., Hartgerink, J. D., & Young, S. W. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1139782 · Cited by 39
“In cancer therapy, tumors can change their microenvironment by manipulating cellular and non-cellular components through complex signaling networks utilizing cytokines, chemokines, and growth factors to allow them to grow and spread (Baghban et al., 2020).”
BackgroundBabajani, A., Eftekharinasab, A., Bekeschus, S., Mehdian, H., Vakhshiteh, F., & Madjd, Z. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03523-x · Cited by 37
“In summary, the interaction between cancer cells and the ECM not only facilitates the conversion of tumor cells into CSCs but also acts as a mechanism for maintaining CSC niches, thereby supporting and preserving specific CSC characteristics [160].”
BackgroundMulti-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies
Salvati, A., Melone, V., Giordano, A., Lamberti, J., Palumbo, D., Palo, L., Rea, D., Memoli, D., Simonis, V., Alexandrova, E., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06856-x · Cited by 40
“The tumor microenvironment (TME), composed of stromal cells, immune cells, and extracellular matrix components, also plays a key role in tumor immune response by regulating the cellular crosstalk [95].”
Lung Cancer Stem Cells—Origin, Diagnostic Techniques and Perspective for Therapies
Raniszewska, A., Kwiecień, I., Rutkowska, E., Rzepecki, P., & Domagala-Kulawik, J. J. (2021) · Cancers · doi:10.3390/cancers13122996 · Cited by 38
“The source of intercellular communication is a complex network of cytokines, chemokines, growth factors, inflammatory mediators and enzymes [82].”
BackgroundThe Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment
Tempest, R., Guarnerio, S., Maani, R., Cooper, J., & Peake, N. (2021) · Cancers · doi:10.3390/cancers13112788 · Cited by 39
“Pathological remodelling of the ECM, which is altered by tumour-induced interactions, is a hallmark of cancer and fibrotic diseases [219].”
BackgroundHong, H. K., Yun, N. H., Jeong, Y., Park, J., Doh, J., Lee, W. Y., & Cho, Y. B. (2021) · Cancer Medicine · doi:10.1002/cam4.4114 · Cited by 37
Cai, N., Lai, A. C. K., Liao, K., Corridon, P. R., Graves, D. J., & Chan, V. (2022) · Polymers · doi:10.3390/polym14091913 · Cited by 34
“Better understanding of basic physical and chemical rate processes will help determine the roles of key biomolecular targets in cell signalling pathways and physiological systems [8].”
BackgroundExploiting the STAT3 Nexus in Cancer-Associated Fibroblasts to Improve Cancer Therapy
Allam, A. H., Yakou, M. H., Pang, L., Ernst, M., & Huynh, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.767939 · Cited by 38
“However, it is now appreciated that non-malignant cells within the tumor microenvironment (TME) play equally important roles in driving the development and progression of tumors (13, 14).”
BackgroundMishra, S. B., Bhatt, T., Kumar, H., Jain, R., Shilpi, S., & Jain, V. K. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1101320 · Cited by 36
“The TME plays an important role in the development and poor prognosis of cancer (Baghban et al., 2020).”
BackgroundTheranostic signature of tumor-derived exosomes in cancer
Kumar, S., Dhar, R., Kumar, L., Shivji, G. G., Jayaraj, R., & Devi, A. (2023) · Medical Oncology · doi:10.1007/s12032-023-02176-6 · Cited by 29
“TEXs are involved in the reprogramming of Cancer Associated Fibroblasts (CAFs) via the TGF/Smad pathway [47], resulting in the transformation of normal epithelial cells into premalignant cells [48, 49].”
BackgroundDailah, H. G., Hommdi, A. A., Koriri, M. D., Algathlan, E. M., & Mohan, S. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e24559 · Cited by 42
“Targeted therapies have the capacity to directly act on cancerous cells via suppressing cell migration, differentiation, and proliferation [10].”
BackgroundInfluentialFu, S., Li, Y., Shen, L., Chen, Y., Lu, J., Ran, Y., Zhao, Y., Tang, H. M., Tan, L., Lin, Q., et al. (2024) · Small · doi:10.1002/smll.202309537 · Cited by 35
Thenuwara, G., Javed, B., Singh, B., & Tian, F. (2024) · Sensors · doi:10.3390/s24092865 · Cited by 37
Zhra, M., Akhund, S. A., & Mohammad, K. S. (2025) · Pharmaceuticals · doi:10.3390/ph18040520 · Cited by 37
“The TME is a complex ecosystem composed of various cell types, including immune cells, fibroblasts, and endothelial cells, along with extracellular matrix components [20].”
Exosomes in inflammation and cancer: from bench to bedside applications
Huang, S., Fang, Y., Qiu, Y., Liu, T., Zhang, W., Yang, Y., Zhong, R., Yang, Y., & Peng, X. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00280-9 · Cited by 46
“Tumor migration and progression are influenced not only by the tumor cells but also by the TME, comprising various non-malignant cells and non-cellular components [107].”
Racacho, K. J., Shiau, Y., Villa, R., Mahri, S., Tang, M., Lin, T., & Li, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1621812 · Cited by 55
“…diverse immune populations — including tumor-in fi ltrating lymphocytes (TILs), macrophages, DCs, and myeloid-derived suppressor cells (MDSCs), as well as non-immune stromal components such as fi broblasts and endothelial cells, all of which work together to modulate anti-tumor immunity (15, 16).”
InfluentialDecellularization of tumours: A new frontier in tissue engineering
García‐Gareta, E., Pérez, M. Á., & García‐Aznar, J. M. (2022) · Journal of Tissue Engineering · doi:10.1177/20417314221091682 · Cited by 34
“6 The attention received by the ECM component of the TME has changed considerably over the last decade as its importance in tumour development, progression and metastasis was discovered.”
Bioinspired and Biomimetic Nanomedicines for Targeted Cancer Therapy
Xu, X., Li, T., & Jin, K. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14051109 · Cited by 37
Казакова, А., Sudarskikh, T., Kovalev, O. I., Kzhyshkowska, J. G., & Larionova, I. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5480 · Cited by 35
“Cells in the TME are involved in recip‐ rocal interaction with tumor cells, which eventually leads to enhanced proliferation, metastasis and chemoresistance (1,3,4).”
BackgroundShin, H., Kim, Y., & Jon, S. (2023) · ACS Nano · doi:10.1021/acsnano.3c00764 · Cited by 38
Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy
Jiang, B., Zhang, W., Zhang, X., & Sun, Y. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.05.002 · Cited by 39
Gui, Z., Ye, Y.-Q., Li, Y., Ren, Z., Wei, N., Liu, L., Wang, H., & Zhang, M. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102001 · Cited by 34
“The tumor microenvironment (TME), which includes a diverse array of cells like tumor cells, immune cells, and cancer-associated fibroblasts (CAFs), plays a pivotal role in tumor progression [8].”
BackgroundZhang, X., Al-Danakh, A., Zhu, X., Feng, D., Yang, L., Wu, H., Li, Y., Wang, S., Chen, Q., & Yang, D. (2024) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10698 · Cited by 36
Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence
Tufail, M., Jiang, C., & Li, N. (2025) · Military Medical Research · doi:10.1186/s40779-025-00595-2 · Cited by 50
Exploring immune checkpoint inhibitors: Focus on PD-1/PD-L1 axis and beyond
Aden, D., Zaheer, S., Sureka, N., Trisal, M., Chaurasia, J. K., & Zaheer, S. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.155864 · Cited by 37
Multimodal Integration in Health Care: Development With Applications in Disease Management
Hao, Y., Cheng, C., Li, J., Li, H., Di, X., Zeng, X., Jin, S., Han, X., Liu, C., Wang, Q., et al. (2025) · Journal of Medical Internet Research · doi:10.2196/76557 · Cited by 44
“The tumor microenvironment (TME) plays a crucial role in tumor initiation, progression, metastasis, and resistance to therapy [23,24].”
Budi, H. S., Izadi, S., Timoshin, A., Asl, S. H., Beyzai, B., Ghaderpour, A., Alian, F., Eshaghi, F. S., Mousavi, S. M., Rafiee, B., et al. (2021) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2021.102373 · Cited by 33
Liu, J., Yi, J., Zhang, Z., et al. (2021) · Aging · doi:10.18632/aging.203173 · Cited by 33
“com 16514 AGING environment is the basis of tumor cell growth, invasion, and drug resistance [5, 6].”
BackgroundQian, H., Fu, Y., Guo, M., Chen, Y., Zhang, D., Wei, Y., Jin, F., Zeng, Q., Wang, Y., Chai, C., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.04.015 · Cited by 37
Méndez-Clemente, A. S., Bravo‐Cuéllar, A., Ochoa, S. G., Santiago‐Mercado, M., Palafox-Mariscal, L. A., Jave‐Suárez, L. F., Ibarra, F. S., Villaseñor-Garcı́a, M. M., Ortiz‐Lazareno, P. C., & Hernández‐Flores, G. (2022) · Oncology Reports · doi:10.3892/or.2022.8349 · Cited by 35
“Furthermore, as reported in other studies, this indicates the key role of IL‐6 and IL‐8 in autocrine signaling for tumor cells and regulation of the immune response against the tumor (31,32).”
ResultLi, M., Zhang, Y., Zhang, X., Liu, Z., Tang, J., Feng, M., Chen, B., Wu, D., & Liu, J. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c14776 · Cited by 34
Computational Approaches in Theranostics: Mining and Predicting Cancer Data
Cova, T. F. G. G., Bento, D. J., & Nunes, S. C. C. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11030119 · Cited by 32
Roles of miRNAs in Colorectal Cancer: Therapeutic Implications and Clinical Opportunities
Mehrgou, A., Ebadollahi, S., Seidi, K., Ayoubi‐Joshaghani, M. H., Ahmadieh-Yazdi, A., Zare, P., Jaymand, M., & Jahanban‐Esfahlan, R. (2020) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2021.029 · Cited by 33
“Therefore, MET process, in which the cells obtain the appearance and the properties of epithelial cells, is the opposite of the EMT process.(4) Regarding drug resistance, though the process has not been fully uncovered yet, it is suggested that it could be caused by the stem- and stem-like cells.”
Self-citationLiquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid
Otsuji, R., Fujioka, Y., Hata, N., Kuga, D., Hatae, R., Sangatsuda, Y., Nakamizo, A., Mizoguchi, M., & Yoshimoto, K. (2024) · Cancers · doi:10.3390/cancers16051009 · Cited by 37
“Furthermore, advances in our understanding of the tumor microenvironment of glioma and advances in immunotherapy have underscored the importance of assessing bodily fluid biomarkers for therapeutic planning and clinical management [30–33].”
BackgroundAmeén, F., Alshehri, W. A., Al-Enazi, N. M., et al. (2020) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2020.1807310 · Cited by 33
Jin, X., Zhang, S., Wang, N., Guan, L., Shao, C., Lin, Y., Liu, J., & Li, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.861601 · Cited by 35
“As a highly complicated system, the TME is composed of various cell types and molecules, including tumor cells, infiltrating immune cells, cancer-associated stromal cells, endothelial cells, and lipocytes, along with some extracellular matrix (ECM) and multiple signaling molecules (14, 15).”
BackgroundCheckpoint Markers and Tumor Microenvironment: What Do We Know?
Ephraim, R., Fraser, S., Nurgali, K., & Apostolopoulos, V. (2022) · Cancers · doi:10.3390/cancers14153788 · Cited by 33
“The dynamic interactions between cancer cells and their microenvironment, which consists of stromal cells (a cellular component) and extracellular matrix components (a non-cellular component), are crucial for promoting the heterogeneity of cancer cells, clonal evolution, and multidrug resistance, which leads to cancer…”
BackgroundFerroptosis As Ultimate Target of Cancer Therapy
Motooka, Y., & Toyokuni, S. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0048 · Cited by 36
Tumor Microenvironment, Radiology, and Artificial Intelligence: Should We Consider Tumor Periphery?
Mohammadi, A., Mirza-Aghazadeh-Attari, M., Faeghi, F., Homayoun, H., Abolghasemi, J., Vogl, T., Bureau, N., Bakhshandeh, M., Acharya, R., & Ardakani, A. A. (2022) · Journal of ultrasound in medicine · doi:10.1002/jum.16086 · Cited by 26
“One of the key concepts introduced recently is the tumor microenvironment (TME), which consists of the principal malignant cells, nonmalignant cells, and extracellular components that enable the bulk of the tumor mass to interact with its surroundings.(1,2) Histopathologic surveys of in vitro and in vivo studies have…”
BackgroundReyes-Avendaño, I., Reyes-Jiménez, E., González-García, K., Pérez-Figueroa, D. C., Baltiérrez‐Hoyos, R., Tapia-Pastrana, G., Sánchez-Chino, X. M., Villa‐Treviño, S., Arellanes‐Robledo, J., & Vásquez-Garzón, V. R. (2022) · Antioxidants · doi:10.3390/antiox11020358 · Cited by 32
“As TME plays a central role in the establishment and progression of HCC, its regulation has been attractive as therapeutic target.”
BackgroundInfluentialIon Channels in Gliomas—From Molecular Basis to Treatment
Elias, A. F., Lin, B. C., & Piggott, B. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032530 · Cited by 33
“Rather, tumor formation and progression are complex processes that involve genetic and epigenetic changes affecting the tumor cells as well as changes in the tumor’s surroundings through mutual and dynamic crosstalk [281].”
Background
Metadata
- Authors
- Baghban, R., Roshangar, L., Jahanban-Esfahlan, R., Seidi, K., Ebrahimi-Kalan, A., Jaymand, M., Kolahian, S., Javaheri, T., & Zare, P.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Kermanshah University of Medical Sciences (IR)
- Universitätsklinikum Tübingen (DE)
- Boston University (US)
- Corresponding author
- Javaheri, Tahereh
- Venue
- Cell Communication and Signaling
- Published
- 2020-04-07
- Volume
- 18
- Issue
- 1
- Pages
- 59-59
- ISSN
- 1478-811X (ISSN-L)
- PMC
- PMC7140346
- OpenAlex
- W3014913757
- Cited by
- 1,784
- References
- 236
- Citations by year
- 2026: 149 · 2025: 328 · 2024: 373 · 2023: 410 · 2022: 318 · 2021: 171 · 2020: 30
- FWCI
- 25.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Communication and Signaling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Instytut Biologii Doswiadczalnej im. M. Nenckiego PAN
- Uniwersytet Kardynała Stefana Wyszyńskiego w Warszawie
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- tumor microenvironment, tumor stroma, extracellular matrix, tumor heterogeneity, clonal evolution, multidrug resistance, metastasis, tumor invasion, cancer diagnosis, 3D tumor models, lab-on-a-chip
- MeSH terms
- Animals, Cell Communication, Extracellular Matrix, Humans, Neoplasms, Stromal Cells, Tumor Microenvironment, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
