The DOI matches its Crossref record; 169 of the 180 references it cites were found in a registry or an index; 3 of the 164 sources its claims cite were checked for support.
Iron as a Central Player and Promising Target in Cancer Progression
Open accessAbstract
Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.
Overview
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TL;DR
This review argues that iron metabolism is reprogrammed in cancer to support proliferation, survival, metastasis, and tumor microenvironment crosstalk, with tumor-associated macrophages acting as iron donors. It highlights therapeutic opportunities including hepcidin/FPN modulation, Tf/TfR targeting, iron chelators, and ferroptosis induction, while noting major clinical validation gaps.
Key findings
- Iron is essential but redox-active; the Fenton reaction produces hydroxyl radicals, causing DNA strand breaks and protein/lipid modifications, while iron-dependent lipid peroxidation drives ferroptosis via glutathione depletion and GPX4 inactivation.
- Cancer cells often increase iron uptake/storage and decrease export: high TfR1, FTL, and IRP-2 correlate with poor prognosis, higher tumor grade, and chemoresistance; low FPN correlates with worse survival, whereas higher FPN correlates with better outcome. Anemia is detected in approximately 40–70% of all cancer patients, linked to TNF-α/IL-6 and iron restriction.
- Tumor-associated macrophages can adopt an iron-release/donor phenotype, including via Lcn-2 and independently of FPN, supporting tumor cell proliferation and growth; anti-inflammatory macrophages show CD163/CD91, HO-1, upregulated FPN, and reduced FT. Excess heme or iron may shift macrophages toward a pro-inflammatory, anti-tumoral phenotype.
- Therapeutic strategies discussed include targeting hepcidin (antibodies/aptamers, BMP/SMAD, IL-6/STAT3), FPN stabilizers, anti-TfR antibodies and drug conjugates, ferritin nanocages, Lcn-2/siderophore pathways, iron chelators (DFO, DFX, Triapine, VLX600), and ferroptosis inducers; no iron chelator used clinically for iron overload has been approved for cancer.
Methods
- Narrative review; no primary experimental data or systematic search is described. It synthesizes published literature on tumor cell iron metabolism, systemic iron homeostasis, TAM biology, and iron-targeting therapies.
- Main analysis is thematic and descriptive, citing mechanistic studies, animal models, and clinical trials; it includes a summary table of pre-clinical studies and clinical trials (Table 1) and a scheme of tumor iron exploitation (Figure 1).
Limitations
- Stated: prospective clinical data for targeting hepcidin are still missing; lack of long-term follow-up studies in cancer patients makes efficacy and safety difficult to predict; no clinically used iron chelator has obtained approval for the cancer setting; targeting iron in the tumor microenvironment remains largely unexplored.
- Stated: mechanisms of Lcn-2 iron handling remain unclear, including how tumor cells selectively take up iron-loaded versus iron-free Lcn-2.
- Evident: as a narrative review, it does not use a systematic search, risk-of-bias assessment, or quantitative synthesis, so conclusions depend on the selected cited literature.
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99 Not checked yet · 31 Own interpretation · 3 No basis given · 1 Partly supported · accuracy not yet measured
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In the paper
“Interestingly, also higher organisms such as fungi or mammals are able of producing this type of iron-scavenging molecules [120,121,122].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Partly supportedcites [120] Bao, 2010, Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex, Nat. Chem. Biol. sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says mammalian cells synthesize low-molecular-weight iron chelators and identifies catechols as metabolites that bind and transport iron. The cited paper does not address fungi producing such molecules, so it supports the mammalian example but not the fungal one. (LLM, conf=0.85)
- Supportedcites [121] Devireddy, 2010, A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in enterobactin production, Cell source
The Results section identifies an iron-binding component of a mammalian siderophore in mouse cells and reports that knocking down the murine enzyme BDH2 eliminates detectable siderophore-associated 2,5-DHBA. This supports the mammalian part of the claim. The paper does not establish siderophore production by fungi; that part is not attributed specifically to this source among the three citations. (LLM, conf=0.91)
- Partly supportedcites [122] Schrettl, 2007, Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection, PLoS Pathog. sourceExperimental — accuracy not yet measured
The Introduction says that the fungus A. fumigatus produces several siderophores. But the Discussion states that siderophore-biosynthesis pathways are absent in mammals, contradicting the mammal part of the claim. Page numbers are not provided in our copy. (LLM, conf=0.91)
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In the paper
“Under these conditions, TAM expressed higher levels of the high-affinity iron-binding protein lipocalin-2 (Lcn-2).”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [66] Mertens, 2018, Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment, Oncoimmunology source
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In the paper
“Recently, we provided evidence that TAM adopt an iron-release phenotype due to their interaction with dying tumor cells, whereby iron availability was increased within the tumor microenvironment [66].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [66] Mertens, 2018, Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment, Oncoimmunology source
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In the paper
“Upon intracellular reduction, (TC3-S)2 is converted to the thiol chelator TC3-SH, which re-programmed macrophages from an iron release to and iron sequestration phenotype [72].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [72] Mertens, C., Akam, E.A., Rehwald, C., Brune, B., Tomat, E., and Jung, M. (2016). Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with Consequences on Tumor Progression. PLoS ONE, 11. source
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In the paper
“While the majority of studies so far focused on mechanisms promoted by tumor cell-derived Lcn-2, recent data from our group suggest that stromal Lcn-2 promoted metastasis by enhancing EMT and lymphangiogenesis [133].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [133] Jung, 2016, Lipocalin 2 from macrophages stimulated by tumor cell-derived sphingosine 1-phosphate promotes lymphangiogenesis and tumor metastasis, Sci. Signal. source
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In the paper
“This is a distinct type of cell death compared to apoptosis, necrosis, or autophagy [5].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [5] Lu, 2017, The Role of Ferroptosis in Cancer Development and Treatment Response, Front. Pharmacol. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The malignant cancer phenotype is often found in association with a deregulated iron homeostasis, particularly the expression of iron-regulated genes that fuel their higher metabolic iron demands needed for division, growth, and survival [10].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [10] Kwok, 2002, The iron metabolism of neoplastic cells: Alterations that facilitate proliferation?, Crit. Rev. Oncol. Hematol. source
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In the paper
“They inhibit erythropoiesis due to iron restriction in the reticuloendothelial system [18].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [18] Buck, 2009, Linking anemia to inflammation and cancer: The crucial role of TNFalpha, Biochem. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“During ferroptosis, a lethal metabolic imbalance arises from glutathione depletion, which inactivates the lipid repair enzyme glutathione-dependent peroxidase 4, GPX4, with the subsequent accumulation of lipid peroxides [6].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [6] NaveenKumar, 2018, The Role of Reactive Oxygen Species and Ferroptosis in Heme-Mediated Activation of Human Platelets, ACS Chem. Biol. source
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In the paper
“On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
What the sources say
- Not checked yetcites [1] Inoue, 1987, Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide, Cancer Res.
- Not checked yetcites [2] Tymoszuk, 2018, Iron in the Tumor Microenvironment-Connecting the Dots, Front. Oncol. source
- Not checked yetcites [3] Thanan, 2012, Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma, Free Radic. Biol. Med. source
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In the paper
“This surplus of iron is needed not only both during early steps of tumor development, e.g., enhanced survival [11] and proliferation of transformed cells [12], but also during late stages to promote the metastatic cascade.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
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In the paper
“Ultimately, tumor cells adjust intracellular iron metabolism to favor iron accumulation, by increasing iron uptake and storage, at the same time decreasing iron export.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This surplus of iron is needed not only both during early steps of tumor development, e.g., enhanced survival [11] and proliferation of transformed cells [12], but also during late stages to promote the metastatic cascade.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [13] Miklasova, 2015, Iron, inflammation and invasion of cancer cells, Clujul. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Mechanistically, cancer-induced anemia is caused by the secretion of inflammatory factors, such as tumor necrosis factor (TNF)-α and interleukin-6 (IL-6).”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [18] Buck, 2009, Linking anemia to inflammation and cancer: The crucial role of TNFalpha, Biochem. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, staining iron deposits, it became apparent that tumors outcompete the natural iron reservoirs in liver and spleen [23].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [23] Freitas, 2007, Iron accumulation in mammary tumor suggests a tug of war between tumor and host for the microelement, Anticancer Res.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
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In the paper
“The amount of the LIP is sensed by post-transcriptional mechanisms of cytosolic iron-regulated RNA binding proteins 1 and 2 (IRP-1 and IRP-2) to fine-tune uptake, storage, and release of iron.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
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In the paper
“Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Simultaneously, iron storage is enhanced by releasing the translational blockade of ferritin (FT) heavy chain (FTH) and FTL.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
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In the paper
“Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
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In the paper
“These findings are of crucial importance since the recycling of senescent RBC by reticuloendothelial macrophages is of utmost importance to recover iron in order to ensure efficient erythropoiesis.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
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In the paper
“Moreover, the homologous TfR2 is also frequently upregulated in cancer cells [29,30].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
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In the paper
“In turn, this may cause a more aggressive tumor cell behavior [1,2,3].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [1] Inoue, 1987, Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide, Cancer Res.
- Not checked yetcites [2] Tymoszuk, 2018, Iron in the Tumor Microenvironment-Connecting the Dots, Front. Oncol. source
- Not checked yetcites [3] Thanan, 2012, Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma, Free Radic. Biol. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Mice fed a low-iron diet prior to implanting tumor cells showed significantly delayed tumor growth [22].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [22] Jian, J., Yang, Q., Shao, Y., Axelrod, D., Smith, J., Singh, B., Krauter, S., Chiriboga, L., Yang, Z., and Li, J. (2013). A link between premenopausal iron deficiency and breast cancer malignancy. BMC Cancer, 13. source
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In the paper
“When intracellular iron is low, IRPs interact with conserved iron-responsive elements (IREs) in the untranslated regions (UTRs) of central genes accounting for iron homeostasis [32,33].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
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In the paper
“A dysfunctional or deregulated iron metabolism in cancer patients often results in a decreased red blood cell (RBC) count [14] and anemia is detected in approximately 40–70% of all cancer patients [15,16].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [14] Ganz, 2009, Iron sequestration and anemia of inflammation, Semin. Hematol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“High TfR1 expression correlated not only with a reduced response to chemotherapy [25], but also increased phosphorylation of src in breast cancer, promoting tumor cell division, motility, and adhesion.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [25] Green, 2017, Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients, Oncotarget source
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In the paper
“Accumulation of iron-dependent lipid modifications promotes a specific form of cell death, known as ferroptosis [4].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [4] Dixon, 2012, Ferroptosis: An iron-dependent form of nonapoptotic cell death, Cell source
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In the paper
“The role of iron for cancer development is tightly linked to its ability to modulate innate and adaptive immune responses of macrophages or T cells.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [51] Nairz, 2014, Iron at the interface of immunity and infection, Front. Pharmacol. source
- Not checked yetcites [52] Schaible, 2004, Iron and microbial infection, Nat. Rev. Microbiol. source
- Not checked yetcites [53] Thevenod, F. (2018). Iron and Its Role in Cancer Defense: A Double-Edged Sword. Met. Ions Life Sci., 18. source
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In the paper
“This iron-donating macrophage phenotype was directly linked to enhanced tumor cell proliferation and growth, both in vitro and in vivo [64,66,67,70,71,72].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [64] Cairo, 2011, Iron trafficking and metabolism in macrophages: Contribution to the polarized phenotype, Trends Immunol. source
- Not checked yetcites [66] Mertens, 2018, Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment, Oncoimmunology source
- Not checked yetcites [67] Recalcati, 2010, Differential regulation of iron homeostasis during human macrophage polarized activation, Eur. J. Immunol. source
- Not checked yetcites [70] Leftin, A., Ben-Chetrit, N., Klemm, F., Joyce, J.A., and Koutcher, J.A. (2017). Iron imaging reveals tumor and metastasis macrophage hemosiderin deposits in breast cancer. PLoS ONE, 12. source
- Not checked yetcites [71] Leftin, 2017, Iron deposition is associated with differential macrophage infiltration and therapeutic response to iron chelation in prostate cancer, Sci. Rep. source
- Not checked yetcites [72] Mertens, C., Akam, E.A., Rehwald, C., Brune, B., Tomat, E., and Jung, M. (2016). Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with Consequences on Tumor Progression. PLoS ONE, 11. source
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In the paper
“These features allow anti-inflammatory macrophages to rapidly mobilize and redistribute iron to the local microenvironment in order to support the demand of surrounding cells.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
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In the paper
“In contrast to the iron sequestration phenotype of inflammatory macrophages induced by pro-inflammatory cytokines and danger-associated molecular patterns (DAMPs), anti-inflammatory macrophages and lymphocytes show an iron release phenotype, donating and distributing iron within the tumor microenvironment.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [50] Marques, O., Porto, G., Rema, A., Faria, F., Cruz Paula, A., Gomez-Lazaro, M., Silva, P., Martins da Silva, B., and Lopes, C. (2016). Local iron homeostasis in the breast ductal carcinoma microenvironment. BMC Cancer, 16. source
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In the paper
“Enhanced hepcidin expression in breast cancer patients points to an autocrine/paracrine regulatory mechanism in order to reduce control local tumor iron efflux [50].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [50] Marques, O., Porto, G., Rema, A., Faria, F., Cruz Paula, A., Gomez-Lazaro, M., Silva, P., Martins da Silva, B., and Lopes, C. (2016). Local iron homeostasis in the breast ductal carcinoma microenvironment. BMC Cancer, 16. source
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In the paper
“Moreover, serum concentrations of FT are increased in cancer patients compared to healthy individuals [35].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [35] Orlandi, 2014, Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer, Ann. Oncol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For this reason, the expression of FT is considered a prognostic marker for some cancer subtypes such as squamous cell carcinoma or breast cancer [27,36,37].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [27] Jezequel, 2012, Validation of tumor-associated macrophage ferritin light chain as a prognostic biomarker in node-negative breast cancer tumors: A multicentric 2004 national PHRC study, Int. J. Cancer source
- Not checked yetcites [36] Weinstein, 1982, Tissue ferritin concentration in carcinoma of the breast, Cancer source
- Not checked yetcites [37] Weinstein, 1989, Tissue ferritin concentration and prognosis in carcinoma of the breast, Breast Cancer Res. Treat. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The inability of FPN to add to iron export under these conditions might be the local expression of hepcidin, which compromises its expression.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
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In the paper
“In invasive tumor areas, iron export via FPN is lower compared to normal tissue, with the notion that FPN expression in carcinomas inversely correlated with patient survival and disease outcome [42].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [42] Pinnix, 2010, Ferroportin and iron regulation in breast cancer progression and prognosis, Sci. Transl. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Pro-inflammatory macrophages are prone to iron retention. They display an iron sequestering phenotype characterized by enhanced iron uptake and storage, but attenuated release [64,65,66,67].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [64] Cairo, 2011, Iron trafficking and metabolism in macrophages: Contribution to the polarized phenotype, Trends Immunol. source
- Not checked yetcites [65] Lane, 2015, Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease, Biochim. Biophys. Acta source
- Not checked yetcites [66] Mertens, 2018, Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment, Oncoimmunology source
- Not checked yetcites [67] Recalcati, 2010, Differential regulation of iron homeostasis during human macrophage polarized activation, Eur. J. Immunol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In cancer patients, hepcidin levels are often elevated, likely because of cancer driven inflammation [48,49].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“As a consequence, tumor cells compete for iron with immune cells of their local microenvironment.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These findings were corroborated by a variety of studies showing ferritin expression mainly in the stromal compartment of tumor tissue [26,27].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [26] Rossiello, 1984, Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue, J. Clin. Pathol. source
- Not checked yetcites [27] Jezequel, 2012, Validation of tumor-associated macrophage ferritin light chain as a prognostic biomarker in node-negative breast cancer tumors: A multicentric 2004 national PHRC study, Int. J. Cancer source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, chronic inflammation or smoldering inflammation often creates an equilibrium between killing of immunogenic tumor cells and immune tolerance, finally driving tumor outgrowth.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [54] Schreiber, 2011, Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These observations suggest the existence of an alternative iron transport pathway in the tumor microenvironment, operating independently of FPN.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“This allows for the uptake of iron-containing heme clusters, which in turn enhances the expression of heme oxygenase 1 (HO-1) [69].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [69] Apte, 2010, Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling, Exp. Hematol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Based on the intimate interplay of tumor cells and tumor-infiltrating immune cells, the latter ones are educated to a tumor-supportive, anti-inflammatory phenotype that significantly promotes tumor neovascularization, metastasis, growth and survival [55].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [55] Zou, 2005, Immunosuppressive networks in the tumour environment and their therapeutic relevance, Nat. Rev. Cancer source
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In the paper
“The expression of FPN is regulated by the acute-phase protein hepcidin, which induces internalization and degradation of FPN upon its binding, thereby attenuating the iron export capacity [43].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [43] Ward, 2007, The molecular mechanism of hepcidin-mediated ferroportin down-regulation, Mol. Biol. Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, the appearance of tumor-supporting, iron-donating immune cells, in particular macrophages, is associated with tumor size and aggressiveness as well as poor patient prognosis [56,57].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [56] Tang, 2013, Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer, Cancer Lett. source
- Not checked yetcites [57] Yu, 2003, Host microenvironment in breast cancer development: Inflammatory and immune cells in tumour angiogenesis and arteriogenesis, Breast Cancer Res. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In fact, a variety of studies confirmed an improved anti-cancer drug uptake upon conjugation to a TfR monoclonal antibody [101,102,103].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [101] Daniels, 2012, The transferrin receptor and the targeted delivery of therapeutic agents against cancer, Biochim. Biophys. Acta source
- Not checked yetcites [102] Xu, 2002, Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes, Mol. Cancer Ther.
- Not checked yetcites [103] Sahoo, 2005, Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention, Mol. Pharm. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It has been observed that human breast tumors contain enhanced amounts of Lcn-2, especially during advanced stages [128].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [128] Bauer, 2008, Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer, Breast Cancer Res. Treat. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“FT nanocages are used to encapsulate chemotherapeutic agents such as doxorubicin [115] or gold ions to induce tumor cell death [116].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [115] Liang, 2014, H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [116] Monti, 2017, Ferritin nanocages loaded with gold ions induce oxidative stress and apoptosis in MCF-7 human breast cancer cells, Dalton Trans. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Binding to the α subunit of ATP synthase, mitochondrial iron uptake is promoted by enterobactin, secreted from commensal bacteria.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [123] Qi, 2018, Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Iron handling in the tumor microenvironment emerged as an important aspect of tumorigenesis.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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 fact that TAMs actively release iron to the tumor microenvironment positions them at the center of pathways associated with the concepts established as the “hallmarks of cancer”.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As the TfR is expressed at high levels at the blood–brain barrier [106,107] due to its physiological function to deliver iron to the brain, it is one of the most studied molecules for receptor-mediated drug delivery to the brain.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [106] Daneman, R., Zhou, L., Agalliu, D., Cahoy, J.D., Kaushal, A., and Barres, B.A. (2010). The mouse blood-brain barrier transcriptome: A new resource for understanding the development and function of brain endothelial cells. PLoS ONE, 5. source
- Not checked yetcites [107] Uchida, 2011, Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors, J. Neurochem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Upregulation of this highly conserved iron acquisition pathway is found in a variety of cancers, including breast and colon [90,91,92,93].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [90] Faulk, 1980, Transferrin and transferrin receptors in carcinoma of the breast, Lancet source
- Not checked yetcites [91] Habashy, 2010, Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen, Breast Cancer Res. Treat. source
- Not checked yetcites [92] Brookes, 2006, Modulation of iron transport proteins in human colorectal carcinogenesis, Gut source
- Not checked yetcites [93] Radulescu, 2012, Luminal iron levels govern intestinal tumorigenesis after Apc loss in vivo, Cell Rep. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, it seems that blocking hepcidin through manipulation of the IL-6 signaling cascade is feasible for the treatment of cancer anemia.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The exceptional capacity to transport drugs across the blood–brain barrier makes the Tf–TfR axis valuable for the treatment of brain tumors through TfR-mediated transcytosis [105].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [105] Dufes, 2013, Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells, Ther. Deliv. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Neutrophils from Lcn-2–/– animals do not migrate to sites of infection and do no longer respond to chemotactic stimuli [124], which however can be reverted by the addition of recombinant Lcn-2 [125].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [125] Schroll, 2012, Lipocalin-2 ameliorates granulocyte functionality, Eur. J. Immunol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interfering with IL-6 signaling using tocilizumab, an antibody directed against the IL-6 receptor was effective in treating chronic anemia associated with arthritis [84].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [84] Song, 2010, Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease, Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additional studies support the idea that excess iron predispose macrophages towards a pro-inflammatory phenotype [79,80], thereby linking macrophage iron handling to their role in inflammatory disease.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [79] Kroner, 2014, TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord, Neuron source
- Not checked yetcites [80] Sindrilaru, 2011, An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice, J. Clin. Investig. source
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“At the same time, these observations raised major concerns for the use of anti-TfR antibodies for the treatment of other tumor types.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“First promising anti-cancer efficacy was recently provided by the simultaneous inhibition of the IL-6 receptor using tocilizumab and the IL-8 receptor by reparixin, showing significantly decreased metastasis of breast cancer cells to the lung, liver, and lymph nodes in a mouse mammary xenograft model [85].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [85] Jayatilaka, 2017, Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration, Nat. Commun. source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Cancer cells reprogram their iron metabolism to increase net iron influx.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Therefore, the Tf–TfR system is considered a promising target to enhance the uptake of drugs that are specifically conjugated to Tf to be recognized by the TfR and to facilitate uptake in, i.e. multidrug-resistant tumor cells [104].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [104] Paterson, 2016, Exploiting transferrin receptor for delivering drugs across the blood-brain barrier, Drug Discov. Today Technol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistently, elevated Lcn-2 levels in the urine of breast cancer patients are correlated with a poor metastatic outcome [129].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [129] Yang, 2009, Lipocalin 2 promotes breast cancer progression, Proc. Natl. Acad. Sci. USA source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, recent findings suggest that excess amounts of heme or iron in hemorrhagic tumor areas are detrimental to the macrophage iron phenotype by shifting the anti-inflammatory, pro-tumor macrophage phenotype to a pro-inflammatory and thus anti-tumoral one [77].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [77] Breckwoldt, 2017, Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages, Front. Immunol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further studies revealed that anti-TfR treatment was specifically encouraging for therapeutic approaches in hematologic cancer due to the fact that cells of the hematopoietic lineage are highly iron-dependent.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, treatment was only effective in some cancers such as adult T-cell leukemia/lymphoma (ATL) and leukemia [99,100].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [99] Kozlowski, 1988, Transferrin receptor expression of AML blasts is related to their proliferative potential, Br. J. Haematol. source
- Not checked yetcites [100] Moura, 2004, A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients, Blood source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Since hepcidin arises as a key iron-regulated gene due to its function as a sensor for systemic iron availability, several strategies are envisioned to manipulate its expression [81].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [81] Gardenghi, 2010, Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“To date, none of the iron chelators employed in the clinic for iron overload disorders has obtained approval for the cancer setting.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, experimental transgenic tumor-bearing mouse mammary tumor virus (PyMT) mice exhibit higher Lcn-2 plasma levels compared to controls, and Lcn-2-deficient PyMT mice developed fewer tumors than Lcn-2-competent littermates [130].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [130] Berger, 2010, Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis, Proc. Natl. Acad. Sci. USA source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, the high hydrophilicity and unfavorable pharmacokinetics of several chelators do not allow reaching effective intratumoral concentrations [59].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [59] Biswas, 2013, Tumor-associated macrophages: Functional diversity, clinical significance, and open questions, Semin. Immunopathol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Cancer cells have a higher demand for iron in order to sustain their proliferative capacity.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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: unclear — It is unclear why the paper says 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
“These observations strengthen the concept that Lcn-2 promotes its pro-tumor functions via Lcn-2R signaling.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
boosteddirect- 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.
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
“Generally, employing metal chelators in the context of cancer treatment remains challenging, when compared to their applications for systemic iron depletion.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, experimental transgenic tumor-bearing mouse mammary tumor virus (PyMT) mice exhibit higher Lcn-2 plasma levels compared to controls, and Lcn-2-deficient PyMT mice developed fewer tumors than Lcn-2-competent littermates [130].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [130] Berger, 2010, Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“For instance, the natural siderophore desferrioxamine (DFO, Desferal®) [134,135] as well as the synthetic chelator derasirox (DFX, Exiade), which are clinically employed to treat iron overload due to chronic blood transfusion therapy [134], and the thiosemicarbazone Triapine® [136,137] have shown promising anti-cancer activity in clinical trials [138].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [134] Kalinowski, 2005, The evolution of iron chelators for the treatment of iron overload disease and cancer, Pharmacol. Rev. source
- Not checked yetcites [135] Dayani, 2004, Desferoxamine (DFO)—Mediated iron chelation: Rationale for a novel approach to therapy for brain cancer, J. Neurooncol. source
- Not checked yetcites [136] Yu, 2006, Chelators at the cancer coalface: Desferrioxamine to Triapine and beyond, Clin. Cancer Res. source
- Not checked yetcites [137] Sutherland, 1981, Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [138] Hatcher, 2009, Synthetic and natural iron chelators: Therapeutic potential and clinical use, Future Med. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Glucose conjugates of several cancer chemotherapeutics, including paclitaxel and doxorubicin [159,160,161], experienced a higher therapeutic efficacy in vivo.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [159] Lin, 2008, Targeting the Delivery of Glycan-Based Paclitaxel Prodrugs to Cancer Cells via Glucose Transporters, J. Med. Chem. source
- Not checked yetcites [160] Liu, 2007, Synthesis of 2′-paclitaxel methyl 2-glucopyranosyl succinate for specific targeted delivery to cancer cells, Bioorg. Med. Chem. Lett. source
- Not checked yetcites [161] Cao, 2013, Targeted Cancer Therapy with a 2-Deoxyglucose-Based Adriamycin Complex, Cancer Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“These approaches exploit overexpression of the glucose transporter GLUT1 in a large fraction of cancer phenotypes [158].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [158] Younes, 1996, Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers, Cancer Res.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Unfortunately, due to serious side effects in several cases, e.g., hearing abnormalities, nephropathy, optic neuropathy, and growth failure in children, their applicability during cancer treatment is hampered [135,139].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [135] Dayani, 2004, Desferoxamine (DFO)—Mediated iron chelation: Rationale for a novel approach to therapy for brain cancer, J. Neurooncol. source
- Not checked yetcites [139] Kontoghiorghes, 2008, Ethical issues and risk/benefit assessment of iron chelation therapy: Advances with deferiprone/deferoxamine combinations and concerns about the safety, efficacy and costs of deferasirox, Hemoglobin source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, especially therapy-resistant and drug-tolerant tumor cells are prone to ferroptosis [164,165].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
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: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 39
- Probably not a substantial claim. 15
In the paper
“Lcn-2 turned out to export iron from TAM, while depletion of the established iron exporter FPN did not alter their iron release capacity [66].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [66] Mertens, 2018, Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment, Oncoimmunology source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Furthermore, cancer-induced anemia as well as inflammation-associated anemia is characterized by reduced erythropoiesis [17].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [17] Nemeth, 2014, Anemia of inflammation, Hematol. Oncol. Clin. N. Am. source
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.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Binding of IRPs to IREs in the 5’-UTR attenuates translation, whereas binding to IREs in the 3’-UTR stabilizes respective mRNAs and fosters translation.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Senescent RBCs are taken up by monocytes in the bloodstream and transported to both liver and spleen.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [24] Theurl, 2016, On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver, Nat. Med. 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Apparently, the expression of different iron-regulated genes such as the transferrin receptor (TfR1) [25], ferritin light chain (FTL) [26,27], and the iron regulatory protein (IRP)-2 [28] in tumor cells correlated with a poor prognosis, a higher tumor grade, and increased chemoresistance.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [25] Green, 2017, Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients, Oncotarget source
- Not checked yetcites [26] Rossiello, 1984, Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue, J. Clin. Pathol. source
- Not checked yetcites [27] Jezequel, 2012, Validation of tumor-associated macrophage ferritin light chain as a prognostic biomarker in node-negative breast cancer tumors: A multicentric 2004 national PHRC study, Int. J. Cancer source
- Not checked yetcites [28] Wang, 2014, IRP2 regulates breast tumor growth, Cancer Res. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“DNA polymerases and helicases contain iron-sulfur groups that rely on iron as essential co-factors [7].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [7] Netz, 2011, Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes, Nat. Chem. Biol. source
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.
In the paper
“Here, iron is crucial in remodeling the extracellular matrix and increasing the motility and invasion of cancer cells [13].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [13] Miklasova, 2015, Iron, inflammation and invasion of cancer cells, Clujul. Med.
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
“Thus, when iron is high, mRNAs of TfR and DMT-1 are unstable and get degraded, which ultimately decreases iron uptake and transport.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
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.
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It may state two separate claims as one.
In the paper
“Interestingly, accumulation of iron-recycling macrophages was exclusively observed in the liver, thus identifying the liver as the main organ for RBC recycling.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [24] Theurl, 2016, On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver, Nat. Med. 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
“Thereby, excess iron that is not utilized, can be stored in the iron storage protein FT and can later be accessed by ferritinophagy [34].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [34] Donfrancesco, 1990, Effects of a single course of deferoxamine in neuroblastoma patients, Cancer Res.
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.
None of the sources cited for this claim have been checked yet.
In the paper
“As a result, iron is potentially mutagenic by causing DNA strand breaks, which provokes cellular transformations, or induces protein as well as lipid modifications within malignant cells.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [1] Inoue, 1987, Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide, Cancer Res.
- Not checked yetcites [2] Tymoszuk, 2018, Iron in the Tumor Microenvironment-Connecting the Dots, Front. Oncol. source
- Not checked yetcites [3] Thanan, 2012, Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma, Free Radic. Biol. Med. source
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.
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
“Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment.”
§ Iron as a Central Player and Promising Target in Cancer Progression > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, cellular iron availability not only controls mitochondrial respiration, but also affects citric acid cycle enzymes [8,9].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
What the sources say
- Not checked yetcites [8] Oexle, 1999, Iron-dependent changes in cellular energy metabolism: Influence on citric acid cycle and oxidative phosphorylation, Biochim. Biophys. Acta source
- Not checked yetcites [9] Volani, 2017, Dietary iron loading negatively affects liver mitochondrial function, Metallomics 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
“Therefore, the Tf/TfR system not only enhances iron uptake, but also provokes tumor cell survival [31].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [31] Jian, 2011, Src regulates Tyr(20) phosphorylation of transferrin receptor-1 and potentiates breast cancer cell survival, J. Biol. Chem. 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
“As a result, RBC recycling and iron storage in liver and spleen are compromised and erythropoiesis is significantly reduced, finally provoking anemia.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 1. Iron and Cancer
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
“These observations were recently underlined by Marques et al., describing an “iron utilization” phenotype of tumor cells, whereas tumor-infiltrating macrophages and lymphocytes represented an “iron donor” phenotype [50].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [50] Marques, O., Porto, G., Rema, A., Faria, F., Cruz Paula, A., Gomez-Lazaro, M., Silva, P., Martins da Silva, B., and Lopes, C. (2016). Local iron homeostasis in the breast ductal carcinoma microenvironment. BMC Cancer, 16. 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, extracellular FT stimulates proliferation of breast cancer cells independently of the iron content, acting as an inflammatory effector mechanism to directly support tumorigenesis [38,39,40].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [38] Mallon, 2000, The basic pathology of human breast cancer, J. Mammary Gland Biol. Neoplasia source
- Not checked yetcites [39] Mantovani, 2008, Cancer-related inflammation, Nature source
- Not checked yetcites [40] Alkhateeb, 2013, Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages, Breast Cancer Res. Treat. 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
“In invasive tumor areas, iron export via FPN is lower compared to normal tissue, with the notion that FPN expression in carcinomas inversely correlated with patient survival and disease outcome [42].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [42] Pinnix, 2010, Ferroportin and iron regulation in breast cancer progression and prognosis, Sci. Transl. Med. source
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
“As alternatively activated macrophages scavenge senescent and/or apoptotic cells [68], they play an important role in tissue repair, regeneration, resolution of inflammation, and iron recycling.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [68] Gregory, 2004, The macrophage and the apoptotic cell: An innate immune interaction viewed simplistically?, Immunology 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, large amounts of hepcidin are found both within the tumor microenvironment and systemically in cancer patients [73,74,75,76].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [73] Tesfay, 2015, Hepcidin regulation in prostate and its disruption in prostate cancer, Cancer Res. source
- Not checked yetcites [74] Miller, 2011, An iron regulatory gene signature predicts outcome in breast cancer, Cancer Res. source
- Not checked yetcites [75] Vela, 2018, Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications, Exp. Mol. Med. source
- Not checked yetcites [76] Zhang, 2014, Disordered hepcidin-ferroportin signaling promotes breast cancer growth, Cell Signal. 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
“The FPN efflux system represents one of the key mechanisms to adjust the iron amount in the body and to affect the ratio of stored and released iron [41].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [41] Donovan, 2005, The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis, Cell Metab. 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 contrast, anti-inflammatory macrophages are predisposed to iron export and the distribution of iron to the extracellular space, whereas iron storage is reduced.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [67] Recalcati, 2010, Differential regulation of iron homeostasis during human macrophage polarized activation, Eur. J. Immunol. source
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.
It may state two separate claims as one.
In the paper
“In addition, macrophages are capable of ferritin secretion, whereby tumor growth is promoted [40].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [40] Alkhateeb, 2013, Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages, Breast Cancer Res. Treat. 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
“The iron-release phenotype is associated with upregulation of the iron exporter FPN, while the iron storage protein FT is downregulated [67].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [67] Recalcati, 2010, Differential regulation of iron homeostasis during human macrophage polarized activation, Eur. J. Immunol. source
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: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Levels of hepcidin are increased during inflammation and decreased by iron insufficiency and erythropoiesis [45,46,47].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
What the sources say
- Not checked yetcites [45] Ganz, 2003, Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation, Blood source
- Not checked yetcites [46] Nemeth, 2009, The role of hepcidin in iron metabolism, Acta Haematol. source
- Not checked yetcites [47] Darshan, 2009, Interacting signals in the control of hepcidin expression, Biometals 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.
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
“Such naturally occurring structures are advantageous over synthetically ones due to their low toxicity and negligible immune responses.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
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: 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies in humans suggest Lcn-2 as a pro-tumorigenic factor in breast cancer, correlating with a decreased survival and reduced responsiveness to neoadjuvant chemotherapy [126,127].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [126] Wenners, A.S., Mehta, K., Loibl, S., Park, H., Mueller, B., Arnold, N., Hamann, S., Weimer, J., Ataseven, B., and Darb-Esfahani, S. (2012). Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer. PLoS ONE, 7. source
- Not checked yetcites [127] Yang, 2013, Lipocalin 2 is a novel regulator of angiogenesis in human breast cancer, FASEB J. source
hedgedcorrelational- 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
“However, no direct correlation of synergistically blocking the IL-6 and IL-8 receptors and hepcidin expression or the effect on cancer-related anemia was reported in this study.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [85] Jayatilaka, 2017, Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration, Nat. Commun. source
plain- 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.
In the paper
“Since FT assembles into spherical cage-like structures and has the potential to reversibly disassemble within cells, it represents an attractive target for nanostructure research in the cancer context [114].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [114] Truffi, 2016, Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer, Pharmacol. Res. 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Phase I trials provided promising results, without any indication of major side effects in patients [97,98].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [97] Brooks, 1995, Phase Ia trial of murine immunoglobulin A antitransferrin receptor antibody 42/6, Clin. Cancer Res.
- Not checked yetcites [98] Taetle, 1986, Mechanisms of growth inhibition by anti-transferrin receptor monoclonal antibodies, Cancer Res.
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
“Siderophores are small, low-molecular-mass iron-binding ligands known from iron acquisition mechanisms used by bacteria [119].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [119] Saha, 2016, Microbial siderophores and their potential applications: A review, Environ. Sci. Pollut. Res. Int. source
plain- 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.
In the paper
“Another consideration is the uptake of secreted FT by the TfR [113].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [113] Li, 2010, Binding and uptake of H-ferritin are mediated by human transferrin receptor-1, Proc. Natl. Acad. Sci. USA source
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.
In the paper
“Neutrophils from Lcn-2–/– animals do not migrate to sites of infection and do no longer respond to chemotactic stimuli [124], which however can be reverted by the addition of recombinant Lcn-2 [125].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [124] Liu, 2013, Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections, J. Immunol. 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
“These observations are somehow mirrored when macrophages are exposed to hemolytic RBCs during e.g., sickle cell anemia [78]. Based on the heme-induced polarization shift, macrophages acquire a more pro-inflammatory phenotype and exacerbate tissue damage [78].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 3. Iron in the Tumor Microenvironment—Role of Tumor-Associated Macrophages
What the sources say
- Not checked yetcites [78] Vinchi, 2016, Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease, Blood 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.
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
“It needs also consideration that cancer cells might have evolved alternative strategies to take up iron trough hitherto-unappreciated transport proteins.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Another aspect of Lcn-2 during infectious diseases is its ability to control neutrophil function [124,125].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
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.
In the paper
“A recent study proposes that bacterial siderophores do not only serve as iron scavengers to limit bacterial growth, but are also able to support the host’s iron homeostasis [123].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [123] Qi, 2018, Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase, Cell source
hedgeddirect- 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. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lcn-2 might accomplish such a role due to its ability to scavenge iron-loaded siderophores [117,118].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [117] Behnsen, J., and Raffatellu, M. (2016). Siderophores: More than Stealing Iron. MBio, 7. source
- Not checked yetcites [118] Smith, 2007, Iron metabolism at the host pathogen interface: Lipocalin 2 and the pathogen-associated iroA gene cluster, Int. J. Biochem. Cell Biol. source
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.
Probably not a substantial 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
“The problem may arise that maturing erythroid cells would severely be affected by anti-TfR antibodies, which, in turn, may disturb erythropoiesis and cause anemia.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
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.
None of the sources cited for this claim have been checked yet.
In the paper
“It can be envisioned that a higher reducing environment in cancer cells, compared to the surrounding tissue, makes reductive activation an attractive strategy to enhance cancer cell specificity [153,154], owing to higher amounts of reduced glutathione compared to healthy, neighboring cells [69].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [153] Akam, 2014, Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators, Metallomics source
- Not checked yetcites [154] Chang, 2013, Disulfide/thiol switches in thiosemicarbazone ligands for redox-directed iron chelation, Dalton Trans. source
- Not checked yetcites [69] Apte, 2010, Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling, Exp. Hematol. source
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.
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
“Because of the stability of disulfide linkages in blood plasma, an advantage of the prochelator strategy is their potential supplementation at high doses, which may foster their uptake by tumor cells, while avoiding unwanted side effects in plasma.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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.
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
“These strategies may also be exerted to achieve selectivity in targeting the iron pool of tumor cells.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“This type of cell death was recently shown to be executed via the tumor suppressor p53 [162,163], suggesting a natural anti-tumor role of ferroptosis.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
hedgeddirect- 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.
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
“Considering that macrophages constitute a major infiltrate in solid tumors and taking their pivotal role in iron metabolism into account, these immune cells are likely a worthwhile target in anti-cancer strategies.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Corroborating the role of Lcn-2, expression of Lcn-2R is also indicative for a poor prognosis, and a reduced survival rate but increased invasion in several cancer entities [131,132].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 4. Strategies to Target Iron Trafficking in the Tumor Microenvironment
What the sources say
- Not checked yetcites [131] Autelitano, F., Loyaux, D., Roudieres, S., Deon, C., Guette, F., Fabre, P., Ping, Q., Wang, S., Auvergne, R., and Badarinarayana, V. (2014). Identification of novel tumor-associated cell surface sialoglycoproteins in human glioblastoma tumors using quantitative proteomics. PLoS ONE, 9. source
- Not checked yetcites [132] Miyamoto, 2011, Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma, Exp. Mol. Pathol. source
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: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Akam et al. explored glucose-conjugated thiosemicarbazone prochelators in colon carcinoma [157], proving enhanced prochelator accumulation in malignant cells.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [157] Akam, 2016, Targeting Iron in Colon Cancer via Glycoconjugation of Thiosemicarbazone Prochelators, Bioconjug. Chem. source
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.
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
“Fundamental to successfully approach chelation therapy in cancer will be the capacity to target iron selectively in malignant cells without affecting normal tissue or the extracellular space.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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.
Probably not a substantial 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
“Chelators derived from bacterial siderophores (e.g., DFO) or other high-affinity scaffolds (e.g., Triapine) lack the required selectivity and thus are not designed to target specifically the higher iron demand of malignant cancer cells, which generally show normal or low systemic iron levels.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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
“More recently, high-throughput screening identified an iron chelating agent as a promising drug candidate for colon cancer (VLX600) [140], which entered a Phase I clinical trial (identifier: NCT02222363) for refractory advanced solid tumors.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [140] Zhang, 2014, Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments, Nat. Commun. 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.
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
“While most studies aim at targeting iron in tumor cells, approaches to addressing iron chelation in cells of the tumor microenvironment is still lacking.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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: 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
“While most of the current chelator-based intervention strategies focus on tumor cells, targeting iron in the tumor microenvironment has not been explored significantly.”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“The use of disulfide bonds as the activation switch of iron prochelators showed encouraging results in vitro, as iron coordination only occurs following intracellular disulfide reduction, leading to the formation of high-affinity tridentate thiolate chelators [153].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 5. Novel Iron Chelation-Based Treatment Strategies
What the sources say
- Not checked yetcites [153] Akam, 2014, Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators, Metallomics 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 paper relies on this without support.
Iron is essential for virtually all organisms.
“Iron is an essential element for virtually all organisms.”
The paper relies on this without support.
Iron is a growth-limiting factor for virtually all organisms.
“Iron is the most abundant element by mass on the Earth and is a growth-limiting factor for virtually all organisms.”
The paper relies on this without support.
There is no excretory route for excess iron.
“Considering the poor bioavailability of iron, the interplay of different proteins involved in iron import, storage, and export has to be tightly regulated, as there is no excretory route for excess iron.”
The paper relies on this without support.
Findings from mouse models of cancer translate to human cancer.
“Mice fed a low-iron diet prior to implanting tumor cells showed significantly delayed tumor growth [22].”
The paper relies on this without support.
In vitro findings about iron handling translate to in vivo tumor behavior.
“This iron-donating macrophage phenotype was directly linked to enhanced tumor cell proliferation and growth, both in vitro and in vivo [64,66,67,70,71,72].”
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?
In the citing paper
“However, in the context of the tumor microenvironment (TME), the situation is quite complicated as M2 TAMs (tumor-infiltrating macrophages) which are “iron-releasing” will support tumor growth while M1 “iron-retaining” limit tumor progression (Jung et al., 2019).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Jung et al., 2019
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
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
“FPN expression in carcinomas inversely correlated with patient survival and disease outcome [42].”
§ Iron as a Central Player and Promising Target in Cancer Progression > 2. Iron Metabolism in Cancer Cells
“an increased expression of FPN in tumor cells correlated with better patient outcome”
Citations
Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · cited 1×
“Accumulation of iron-dependent lipid modifications promotes a specific form of cell death, known as ferroptosis [4].”
BackgroundMantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474 · cited 2×
“Outgrowth is supported as tumor cells often evade im une recognition or even acquire an immunosuppressive phenotype [54].”
BackgroundTargeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803 · cited 1×
“Tissue sequestration and systemic iron levels are regulated by hepcidin, by controlling FPN-facilitated iron release into the plasma of all cells that handle iron, including intestinal enterocytes, hepatocytes, and macrophages [44].”
BackgroundFerroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398 · cited 1×
“shown to be executed via the tumor suppressor p53 [162,163], suggesting a natural anti-tumor role of ferroptosis.”
BackgroundTwo to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120 · cited 1×
“When intracellular iron is low, IRPs interact with conserved iron-responsive elements (IREs) in the untranslated regions (UTRs) of central genes accounting for iron homeostasis [32,33].”
BackgroundImmunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057 · cited 1×
“tumor cells and tumor-infiltrating immune cells, the latter ones are educated to a tumor-supportive, anti-inflammatory phenotype that significantly promotes tumor neovascularization, metastasis, growth and survival [55].”
BackgroundDependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway
Viswanathan, V. S., Ryan, M. J., Dhruv, H. D., Gill, S., Eichhoff, O. M., Seashore-Ludlow, B., Kaffenberger, S. D., Eaton, J. K., Shimada, K., Aguirre, A. J., et al. (2017) · Nature · doi:10.1038/nature23007 · Cited by 2,011
Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition
Hangauer, M. J., Viswanathan, V. S., Ryan, M. J., Bole, D., Eaton, J. K., Matov, A., Galeas, J., Dhruv, H. D., Berens, M. E., Schreiber, S. L., et al. (2017) · Nature · doi:10.1038/nature24297 · Cited by 1,799
Cited by
Sorted by citations
Kumthekar, P., Ko, C. H., Paunesku, T., Dixit, K., Sonabend, A. M., Bloch, O. G., Tate, M. C., Schwartz, M. A., Zuckerman, L., Lezon, R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abb3945 · Cited by 368
“The majority of Au was found associated with the Zn-rich vasculature (XFM maps of RBCs show particularly high Zn, although this element is also found in leukocytes and plasma), as well as in Fe-positive cells, in particular tumor-associated macrophages, which represent a critical source of Fe within the tumor microenv…”
BackgroundThe Role of Iron Regulation in Immunometabolism and Immune-Related Disease
Cronin, S. J. F., Woolf, C. J., Weiss, G., & Penninger, J. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00116 · Cited by 299
“However, in the context of the tumor microenvironment (TME), the situation is quite complicated asM2 TAMs (tumor-infiltratingmacrophages) which are “iron-releasing” will support tumor growth while M1 “iron-retaining” limit tumor progression (Jung et al., 2019).”
BackgroundAltered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology
Brown, R. A. M., Richardson, K. L., Kabir, T. D., Trinder, D., Ganß, R., & Leedman, P. J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00476 · Cited by 284
Targeting iron metabolism in cancer therapy
Morales, M., & Xue, X. (2021) · Theranostics · doi:10.7150/thno.59092 · Cited by 262
“which consequently demands a greater amount of iron and results in dysregulated levels of key proteins involved in iron metabolism [38, 39].”
BackgroundMolecular and Cellular Functions of CTLA-4
Coillie, S. V., Wiernicki, B., & Xu, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3266-5_2 · Cited by 259
Metadata
- Authors
- Jung, M., Mertens, C., Tomat, E., & Brüne, B.
- Affiliations
- Goethe University Frankfurt (DE)
- University of Arizona (US)
- Corresponding author
- Brüne, Bernhard
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2019-01-11
- Volume
- 20
- Issue
- 2
- Pages
- 273
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC6359419
- OpenAlex
- W2910083100
- Semantic Scholar
- 714cc6f101914382c4609796c780897112029c2e
- Cited by
- 268
- References
- 180
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 32 · 2023: 39 · 2022: 58 · 2021: 50 · 2020: 33 · 2019: 12
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB815)
- Wilhelm Sander-Stiftung (2017.130.1)
- National Institutes of Health (GM127646)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- iron metabolism, tumor progression, tumor microenvironment, tumor-associated macrophages, iron homeostasis, oxidative stress, metastasis, iron acquisition, iron export, iron storage, cancer therapy, redox biology
- MeSH terms
- Antineoplastic Agents, DNA Damage, Humans, Iron, Neoplasms, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Oxidative Stress, Disease Progression, Metabolic Networks and Pathways, Tumor Microenvironment
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 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (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 ›
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