Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth
Open accessAbstract
Extracellular matrix (ECM) is an essential and dynamic component of all tissues and directly affects cellular behavior by providing both mechanical and biochemical signaling cues. Changes in ECM can alter tissue homeostasis, potentially leading to promotion of cellular transformation and the generation of tumors. Therefore, understanding ECM compositional changes during cancer progression is vital to the development of targeted treatments. Previous efforts to reproduce the native 3D cellular microenvironment have utilized protein gels and scaffolds that incompletely recapitulate the complexity of native tissues. Here, we address this problem by extracting and comparing ECM from normal human colon and colon tumor that had metastasized to liver. We found differences in protein composition and stiffness, and observed significant differences in vascular network formation and tumor growth in each of the reconstituted matrices, both in vitro and in vivo. We studied free/bound ratios of NADH in the tumor and endothelial cells using Fluorescence Lifetime Imaging Microscopy as a surrogate for the metabolic state of the cells. We observed that cells seeded in tumor ECM had higher relative levels of free NADH, consistent with a higher glycolytic rate, than those seeded in normal ECM. These results demonstrate that the ECM plays an important role in the growth of cancer cells and their associated vasculature.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Complex components of the tumor microenvironment can significantly affect the growth and metastasis of cancer via mechanical and biochemical factors.
“Various studies have demonstrated that complex components can significantly affect the growth and metastasis of cancer via mechanical and biochemical factors113–116.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [116]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · see citing works
Universal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352 · see citing works
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744 · see citing works
An overview of tissue and whole organ decellularization processes
Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.057 · Cited by 3,591 · see citing works
The extracellular matrix: A dynamic niche in cancer progression
Lu, P., Weaver, V. M., & Werb, Z. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201102147 · Cited by 3,024 · see citing works
Bissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180 · see citing works
A tense situation: forcing tumour progression
Butcher, D. T., Alliston, T. N., & Weaver, V. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2544 · Cited by 1,922 · see citing works
Extracellular matrix as a biological scaffold material: Structure and function
BADYLAK, S., FREYTES, D., & GILBERT, T. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2008.09.013 · Cited by 1,671 · see citing works
Reprint of: Extracellular matrix as a biological scaffold material: Structure and function
Badylak, S. F., Freytes, D. O., & Gilbert, T. W. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.07.016 · Cited by 1,361 · see citing works
The Phasor Approach to Fluorescence Lifetime Imaging Analysis
Digman, M. A., Caiolfa, V. R., Zamai, M., & Gratton, E. (2007) · Biophysical Journal · doi:10.1529/biophysj.107.120154 · Cited by 1,150 · see citing works
Self-citationThe nanomechanical signature of breast cancer
Plodinec, M., Loparić, M., Monnier, C. A., Obermann, E. C., Zanetti‐Dällenbach, R., Oertle, P., Hyötylä, J. T., Aebi, U., Bentires‐Alj, M., Lim, R. Y. H., et al. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.167 · Cited by 1,111 · see citing works
PETERSEN, O. W., Rønnov‐Jessen, L., Howlett, A. R., & Bissell, M. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9064 · Cited by 1,096 · see citing works
Kenny, P. A., Lee, G. Y., Myers, C. A., Neve, R. M., Semeiks, J. R., Spellman, P. T., Lorenz, K., Lee, E. H., Barcellos‐Hoff, M. H., PETERSEN, O. W., et al. (2008) · eScholarship (California Digital Library) · Cited by 1,039 · see citing works
Targeting cellular metabolism to improve cancer therapeutics
Zhao, Y., Butler, E. B., & Tan, M. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.60 · Cited by 994 · see citing works
Dynamic interplay between the collagen scaffold and tumor evolution
Egeblad, M., Rasch, M. G., & Weaver, V. M. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.08.015 · Cited by 898 · see citing works
Xiong, G., Deng, L., Zhu, J., Rychahou, P. G., & Xu, R. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-1 · Cited by 756 · see citing works
Biosynthetic hydrogel scaffolds made from fibrinogen and polyethylene glycol for 3D cell cultures
Almany, L., & Seliktar, D. (2004) · Biomaterials · doi:10.1016/j.biomaterials.2004.06.047 · Cited by 553 · see citing works
Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix
Freytes, D. O., Martin, J. D., Velankar, S., Lee, A. S., & Badylak, S. F. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2007.12.014 · Cited by 531 · see citing works
In vivo vasculogenic potential of human blood-derived endothelial progenitor cells
Melero‐Martin, J. M., Khan, Z. A., Picard, A., Wu, X. W., Paruchuri, S. M., & Bischoff, J. E. (2007) · Blood · doi:10.1182/blood-2006-12-062471 · Cited by 502 · see citing works
Newman, A. C., Nakatsu, M. N., Chou, W., Gershon, P. D., & Hughes, C. C. W. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-05-0393 · Cited by 492 · see citing works
Self-citationWnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer
Pate, K. T., Stringari, C., Sprowl‐Tanio, S., Wang, K., TeSlaa, T., Hoverter, N. P., McQuade, M. M., Garner, C., Digman, M. A., Teitell, M. A., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201488598 · Cited by 459 · see citing works
Self-citationPickl, M., & Ries, C. H. (2008) · Oncogene · doi:10.1038/onc.2008.394 · Cited by 403 · see citing works
Longati, P., Jia, X., Eimer, J., Wagman, A., Witt, M.-R., Rehnmark, S., Verbeke, C., Toftgård, R., Löhr, M., & Heuchel, R. L. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-95 · Cited by 394 · see citing works
3D microtumors in vitro supported by perfused vascular networks
Sobrino, A., Phan, D. T. T., Datta, R., Wang, X., Hachey, S. J., Romero-López, M., Gratton, E., Lee, A. P., George, S. C., & Hughes, C. C. W. (2016) · Scientific Reports · doi:10.1038/srep31589 · Cited by 387 · see citing works
Self-citationCancer cell angiogenic capability is regulated by 3D culture and integrin engagement
Fischbach, C., Kong, H. J., Hsiong, S. X., Evangelista, M. B., Yuen, W. W., & Mooney, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808932106 · Cited by 312 · see citing works
3-D Tumor Model forIn VitroEvaluation of Anticancer Drugs
Horning, J. L., Sahoo, S. K., Vijayaraghavalu, S., Dimitrijevic, S., Vasir, J. K., Jain, T. K., Panda, A. K., & Labhasetwar, V. D. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800047v · Cited by 292 · see citing works
In situforce mapping of mammary gland transformation
Lopez, J. I., Kang, I., You, W., McDonald, D. M., & Weaver, V. M. (2011) · Integrative Biology · doi:10.1039/c1ib00043h · Cited by 284 · see citing works
Tumor Angiogenesis: A Possible Control Point in Tumor Growth
Folkman, J. (1975) · Annals of Internal Medicine · doi:10.7326/0003-4819-82-1-96 · Cited by 279 · see citing works
Maintenance of Human Hepatocyte Function In Vitro by Liver-Derived Extracellular Matrix Gels
Sellaro, T. L., Ranade, A. R., Faulk, D. M., McCabe, G. P., Dorko, K., Badylak, S. F., & Strom, S. C. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0587 · Cited by 276 · see citing works
Naba, A., Clauser, K. R., Whittaker, C. A., Carr, S. A., Tanabe, K. K., & Hynes, R. O. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-518 · Cited by 238 · see citing works
Chapter 4 An Optimized Three‐Dimensional In Vitro Model for the Analysis of Angiogenesis
Nakatsu, M. N., & Hughes, C. C. W. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)02004-1 · Cited by 236 · see citing works
Self-citationThe effect of detergents on the basement membrane complex of a biologic scaffold material
Faulk, D. M., Carruthers, C. A., Warner, H. J., Kramer, C. R., Reing, J. E., Zhang, L., D’Amore, A., & Badylak, S. F. (2013) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.09.006 · Cited by 220 · see citing works
Bauer, A. L., Jackson, T. L., & Jiang, Y. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000445 · Cited by 216 · see citing works
Injectable hydrogel scaffold from decellularized human lipoaspirate
Young, D. A., Ibrahim, D. O., Hu, D. P., & Christman, K. L. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.09.035 · Cited by 213 · see citing works
Extracellular Matrix Stiffness and Architecture Govern Intracellular Rheology in Cancer
Baker, E. L., Bonnecaze, R. T., & Zaman, M. H. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.05.054 · Cited by 203 · see citing works
Stringari, C., Nourse, J. L., Flanagan, L. A., & Gratton, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048014 · Cited by 197 · see citing works
Koh, W., Stratman, A. N., Sacharidou, A., & Davis, G. E. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)02005-3 · Cited by 193 · see citing works
Serebriiskii, I. G., Castelló-Cros, R., Lamb, A., Golemis, E. A., & Cukierman, E. (2008) · Matrix Biology · doi:10.1016/j.matbio.2008.02.008 · Cited by 176 · see citing works
Tube Formation: an In Vitro Matrigel Angiogenesis Assay
Ponce, M. L. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-241-0_10 · Cited by 154 · see citing works
Fong, A. H., Romero-López, M., Heylman, C. M., Keating, M., Tran, D. D., Sobrino, A., Tran, A. Q., Pham, H. H., Fimbres, C., Gershon, P. D., et al. (2016) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0027 · Cited by 140 · see citing works
Self-citationObberghen‐Schilling, E. V., Tucker, R. P., Saupe, F., Gasser, I., Cseh, B., & Orend, G. (2011) · The International Journal of Developmental Biology · doi:10.1387/ijdb.103243eo · Cited by 126 · see citing works
Tumor mechanics and metabolic dysfunction
Tung, J. C., Barnes, J. M., Desai, S. R., Sistrunk, C., Conklin, M. W., Schedin, P. S., Eliceiri, K. W., Keely, P. J., Seewaldt, V. L., & Weaver, V. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.11.020 · Cited by 124 · see citing works
Biomechanical and biochemical characteristics of a human fibroblast-produced and remodeled matrix
Ahlfors, J.-E. W., & Billiar, K. L. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2006.12.030 · Cited by 117 · see citing works
Michaylira, C. Z., Wong, G. S., Miller, C. G., Gutierrez, C. M., Nakagawa, H., Hammond, R., Klein-Szanto, A. J., Lee, J.-S., Kim, S. B., Herlyn, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0704 · Cited by 117 · see citing works
A recellularized human colon model identifies cancer driver genes
Chen, H. J., Wei, Z., Sun, J. M., Bhattacharya, A., Savage, D. J., Serda, R. E., Mackeyev, Y., Curley, S. A., Bu, P., Wang, L., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3586 · Cited by 99 · see citing works
Baiguera, S., Gaudio, C. D., Jaus, M. O., Polizzi, L., Gonfiotti, A., Comin, C., Bianco, A., Ribatti, D., Taylor, D. A., & Macchiarini, P. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.01.064 · Cited by 93 · see citing works
Concentration Independent Modulation of Local Micromechanics in a Fibrin Gel
Kotlarchyk, M. A., Shreim, S., Alvarez‐Elizondo, M. B., Estrada, L. C., Singh, R. K., Valdevit, L., Kniazeva, E., Gratton, E., Putnam, A. J., & Botvinick, E. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020201 · Cited by 88 · see citing works
Self-citationA novel tissue engineered three-dimensional in vitro colorectal cancer model
Nyga, A., Loizidou, M., Emberton, M., & Cheema, U. (2013) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.04.028 · Cited by 83 · see citing works
Preparation and characterization of a biologic scaffold from esophageal mucosa
Keane, T. J., Londoño, R., Carey, R. M., Carruthers, C. A., Reing, J. E., Dearth, C. L., D’Amore, A., Medberry, C. J., & Badylak, S. F. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.05.052 · Cited by 76 · see citing works
Irvine, S. M., Cayzer, J., Todd, E. M., Lun, S., Floden, E. W., Negron, L., Fisher, J. N., Dempsey, S. G., Alexander, A., Hill, M. C., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.05.040 · Cited by 73 · see citing works
mTORC2 mediates CXCL12-induced angiogenesis
Ziegler, M. E., Hatch, M. M. S., Wu, N., Muawad, S. A., & Hughes, C. C. W. (2016) · Angiogenesis · doi:10.1007/s10456-016-9509-6 · Cited by 68 · see citing works
Self-citationPathak, A., & Kumar, S. (2013) · Integrative Biology · doi:10.1039/c3ib40017d · Cited by 59 · see citing works
Seaman, M. E., Peirce, S. M., & Kelly, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020807 · Cited by 57 · see citing works
The role of engineering approaches in analysing cancer invasion and metastasis
Zaman, M. H. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3564 · Cited by 57 · see citing works
The quantification of vascular beds: A stereological approach
Dockery, P., & Fraher, J. (2007) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2006.12.011 · Cited by 48 · see citing works
Liver-metastatic potential of colorectal cancer is related to the stromal composition of the tumour.
Nyström, H., Naredi, P. L. J., Berglund, A., Palmqvist, R., Tavelin, B., & Sund, M. (2012) · PubMed · Cited by 43 · see citing works
White, S. M., George, S. C., & Choi, B. (2011) · Microvascular Research · doi:10.1016/j.mvr.2011.03.006 · Cited by 31 · see citing works
(2009) · Methods in molecular biology · doi:10.1007/978-1-59745-241-0 · Cited by 28 · see citing works
Alves, T. R., da Fonseca, A. C. C., Nunes, S. S., de Barros, A. O. D. S., Dubois, L. G., Faria, J., Kahn, S. A., Viana, N. B., de Souza, J. M., Legrand, C., et al. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.06.006 · Cited by 24 · see citing works
Concentration independent modulation of local micromechanics in a fibrin clot
Kotlarchyk, M. A., Shreim, S., Alvarez‐Elizondo, M. B., & Botvinick, E. L. (2011) · Optics in the Life Sciences · doi:10.1364/ota.2011.otmc6 · Cited by 23 · see citing works
Self-citationNarrow-Banding Images and Structures of Microvessels of Colonic Lesions
Mizuno, K., Kudo, S., Ohtsuka, K., Hamatani, S., Wada, Y., Inoue, H., & Aoyagi, Y. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-010-1519-4 · Cited by 13 · see citing works
Deep tissue imaging by enhanced photon collection
Crosignani, V., Jahid, S., Dvornikov, A. S., & Gratton, E. (2014) · Journal of Innovative Optical Health Sciences · doi:10.1142/s1793545814500345 · Cited by 7 · see citing works
Kenny, P. A., Lee, G. Y., Myers, C. A., Neve, R. M., Semeiks, J. R., Spellman, P. T., Lorenz, K., Lee, E. H., Barcellos-Hoff, M. H., Petersen, O. W., et al. (2007) · Molecular Oncology · doi:10.1016/j.molonc.2007.02.004 · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 64 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [59]Serebriiskii I Castelló-Cros R Lamb A Golemis EA Cukierman E Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells Matrix Biology 2008 27 573 585 18411046 PMC2603546
Cited by
Sorted by citations
The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer
Senthebane, D. A., Rowe, A., Thomford, N. E., Shipanga, H., Munro, D., Mazeedi, M. A. M. A., Almazyadi, H. A. M., Kallmeyer, K., Dandara, C., Pepper, M. S., et al. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071586 · Cited by 400 · see citing works
Scaffold-based 3D cell culture models in cancer research
Abuwatfa, W. H., Pitt, W. G., & Husseini, G. A. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-00994-y · Cited by 347 · see citing works
Obesity, Diabetes, and Increased Cancer Progression
Kim, D.-S., & Scherer, P. E. (2021) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2021.0077 · Cited by 312 · see citing works
Tumor-on-a-chip: from bioinspired design to biomedical application
Liu, X., Fang, J., Huang, S., Wu, X., Xie, X., Wang, J., Liu, F., Zhang, M., Peng, Z., & Hu, N. (2021) · Microsystems & Nanoengineering · doi:10.1038/s41378-021-00277-8 · Cited by 246 · see citing works
Engineering Vascularized Organoid-on-a-Chip Models
Shirure, V. S., Hughes, C. C. W., & George, S. C. (2021) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-090120-094330 · Cited by 197 · see citing works
Self-citationOrganoid models of gastrointestinal cancers in basic and translational research
Lau, H. C.-H., Kranenburg, O., Xiao, H., & Yu, J. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0255-2 · Cited by 195 · see citing works
Brauchle, E., Kasper, J., Daum, R., Schierbaum, N., Falch, C., Kirschniak, A., Schäffer, T. E., & Schenke‐Layland, K. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.03.016 · Cited by 182 · see citing works
The cancer matrisome: From comprehensive characterization to biomarker discovery
Socovich, A. M., & Naba, A. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.06.005 · Cited by 158 · see citing works
Decellularized Extracellular Matrix for Bioengineering Physiomimetic 3D in Vitro Tumor Models
Ferreira, L. P., Gaspar, V. M., & Mano, J. F. (2020) · Trends in Biotechnology · doi:10.1016/j.tibtech.2020.04.006 · Cited by 153 · see citing works
Tumor organoid models in precision medicine and investigating cancer-stromal interactions
Xu, R., Zhou, X., Wang, S., & Trinkle, C. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107668 · Cited by 134 · see citing works
Applications of tumor chip technology
Hachey, S. J., & Hughes, C. C. W. (2018) · Lab on a Chip · doi:10.1039/c8lc00330k · Cited by 128 · see citing works
Self-citationHachey, S. J., Movsesyan, S., Nguyen, Q. H., Burton-Sojo, G., Tankazyan, A., Wu, J., Hoang, T., Zhao, D., Wang, S., Hatch, M. M., et al. (2021) · Lab on a Chip · doi:10.1039/d0lc01216e · Cited by 124 · see citing works
Self-citationDecellularized Extracellular Matrix for Cancer Research
Hoshiba, T. (2019) · Materials · doi:10.3390/ma12081311 · Cited by 116 · see citing works
Exploring the extracellular matrix in health and disease using proteomics
Taha, I. N., & Naba, A. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190001 · Cited by 100 · see citing works
Targeting the Tumor Microenvironment in Colorectal Peritoneal Metastases
Ceelen, W. P., Ramsay, R. G., Narasimhan, V., Heriot, A. G., & Wever, O. D. (2020) · Trends in cancer · doi:10.1016/j.trecan.2019.12.008 · Cited by 93 · see citing works
Peela, N., Truong, D. D., Saini, H., Chu, H., Mashaghi, S., Ham, S. L., Singh, S. K., Tavana, H., Mosadegh, B., & Nikkhah, M. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.04.017 · Cited by 92 · see citing works
Li, M., Xi, N., Wang, Y., & Liu, L. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0494-3 · Cited by 86 · see citing works
Bauleth-Ramos, T., Feijão, T., Gonçalves, A., Shahbazi, M.-A., Liu, Z., Barrias, C., Oliveira, M. J., Granja, P., Santos, H. A., & Sarmento, B. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.025 · Cited by 79 · see citing works
Addressing Patient Specificity in the Engineering of Tumor Models
Bray, L. J., Hutmacher, D. W., & Bock, N. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00217 · Cited by 76 · see citing works
Organ on Chip Technology to Model Cancer Growth and Metastasis
Imparato, G., Urciuolo, F., & Netti, P. A. (2022) · Bioengineering · doi:10.3390/bioengineering9010028 · Cited by 76 · see citing works
Extracellular Matrix Bioscaffolds for Building Gastrointestinal Tissue
Hussey, G. S., Cramer, M. C., & Badylak, S. F. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.09.004 · Cited by 69 · see citing works
Bao, M., Chen, Y., Liu, J.-T., Bao, H., Wang, W.-B., Qi, Y.-X., & Lv, F. (2021) · Angiogenesis · doi:10.1007/s10456-021-09804-7 · Cited by 59 · see citing works
D’Angelo, E., Natarajan, D., Sensi, F., Ajayi, O., Fassan, M., Mammano, E., Pilati, P., Pavan, P. G., Bresolin, S., Preziosi, M., et al. (2020) · Cancers · doi:10.3390/cancers12020364 · Cited by 65 · see citing works
Bahrami, A., Hassanian, S. M., Khazaei, M., Hasanzadeh, M., Shahidsales, S., Maftouh, M., Ferns, G. A., & Avan, A. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26183 · Cited by 64 · see citing works
Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids
Moura, B. S., Monteiro, M. V., Ferreira, L. P., Lavrador, P., Gaspar, V. M., & Mano, J. F. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202202825 · Cited by 63 · see citing works
Reproducible extracellular matrices for tumor organoid culture: challenges and opportunities
Li, K., He, Y., Jin, X., Jin, K., & Qian, J. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06349-x · Cited by 68 · see citing works
Engineering in vitro models of hepatofibrogenesis
Mazza, G., Al‐Akkad, W., & Rombouts, K. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.018 · Cited by 59 · see citing works
Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies
Bouquerel, C., Dubrova, A., Hofer, I., Phan, D. T. T., Bernheim, M., Ladaigue, S., Cavaniol, C., Maddalo, D., Cabel, L., Mechta-Grigoriou, F., et al. (2023) · Lab on a Chip · doi:10.1039/d3lc00531c · Cited by 58 · see citing works
Keating, M., Kurup, A., Alvarez‐Elizondo, M. B., Levine, A. J., & Botvinick, E. L. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.05.008 · Cited by 58 · see citing works
Self-citationAzadi, S., Es, H. A., Bazaz, S. R., Thiery, J. P., Asadnia, M., & Warkiani, M. E. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118526 · Cited by 58 · see citing works
Mechanism of ECM-induced dormancy and chemoresistance in A549 human lung carcinoma cells
Keeratichamroen, S., Lirdprapamongkol, K., & Svasti, J. (2018) · Oncology Reports · doi:10.3892/or.2018.6258 · Cited by 56 · see citing works
Karlsson, S., & Nyström, H. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103712 · Cited by 54 · see citing works
Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment
Micek, H. M., Visetsouk, M. R., Masters, K. S. B., & Kreeger, P. K. (2020) · iScience · doi:10.1016/j.isci.2020.101742 · Cited by 53 · see citing works
Martin, S. Z., Wagner, D., Hörner, N., Horst, D. A., Lang, H., Tagscherer, K. E., & Roth, W. (2019) · BMC Cancer · doi:10.1186/s12885-019-6270-4 · Cited by 49 · see citing works
Tsai, Y., Tseng, L., Hsu, C., Yang, M., Chiu, J., & Shyr, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178173 · Cited by 48 · see citing works
Morris, A. H., Lee, H., Xing, H., Stamer, D. K., Tan, M., & Kyriakides, T. R. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b08920 · Cited by 46 · see citing works
Nanoemulsions as Effective Carriers for the Treatment of Lung Cancer
Choudhury, H., Pandey, M., Gorain, B., Chatterjee, B., Madheswaran, T., Md, S., Mak, K., Tambuwala, M. M., Chourasia, M. K., & Kesharwani, P. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815720-6.00009-5 · Cited by 46 · see citing works
Extracellular Matrix-Based Hydrogels to Tailoring Tumor Organoids
Lee, H. J., Mun, S., Pham, D. M., & Kim, P. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01801 · Cited by 43 · see citing works
Applications of lung cancer organoids in precision medicine: from bench to bedside
Li, H., Chen, Z., Chen, N., Fan, Y., Xu, Y., & Xu, X. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01332-9 · Cited by 43 · see citing works
The vascular niche in next generation microphysiological systems
Ewald, M. L., Chen, Y.-H., Lee, A. P., & Hughes, C. C. W. (2021) · Lab on a Chip · doi:10.1039/d1lc00530h · Cited by 40 · see citing works
Self-citationKlabukov, I., Smirnova, A., Yakimova, A. O., Kabakov, A. E., Atiakshin, D., Petrenko, D. А., Shestakova, V. A., Sulina, Y. Y., Yatsenko, E., Stepanenko, V. N., et al. (2024) · Journal of Molecular Pathology · doi:10.3390/jmp5040029 · Cited by 40 · see citing works
Individual Susceptibility Analysis Using Patient-derived Slice Cultures of Colorectal Carcinoma
Sönnichsen, R., Hennig, L., Blaschke, V., Winter, K., Körfer, J., Haehnel, S., Monecke, A., Wittekind, C., Jansen‐Winkeln, B., Thieme, R., et al. (2017) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2017.11.002 · Cited by 36 · see citing works
Yang, Y., Lin, Q., Zhou, C., Li, Q., Li, Z., Cao, Z., Liang, J., Li, H., Mei, J., Zhang, Q., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00250 · Cited by 36 · see citing works
Decellularized normal and cancer tissues as tools for cancer research
Gentilin, E., D’Angelo, E., Agostini, M., & Astolfi, L. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-021-00398-2 · Cited by 36 · see citing works
Decellularization of tumours: A new frontier in tissue engineering
García‐Gareta, E., Pérez, M. Á., & García‐Aznar, J. M. (2022) · Journal of Tissue Engineering · doi:10.1177/20417314221091682 · Cited by 35 · see citing works
Yang, Z., Xue, F. S., Li, M., Zhu, X., Lu, X., Wang, C., Xu, E., Wang, X., Zhang, L., Heng, Y., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.753330 · Cited by 34 · see citing works
Marques-Magalhães, Â., Cruz, T., Costa, Â. M., Estêvão, D., Rios, E., Canão, P. A., Velho, S., Carneiro, F., Oliveira, M. J., & Cardoso, A. P. (2022) · Cancers · doi:10.3390/cancers14020359 · Cited by 31 · see citing works
Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
Mun, S., Lee, H. J., & Kim, P. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01191-5 · Cited by 31 · see citing works
Tseng, L., Chiu, J., Liu, C., Tsai, Y., Wang, Y.-L., Yang, C., & Shyr, Y. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4195-7 · Cited by 30 · see citing works
Stem cell-based vascularization of microphysiological systems
Browne, S., Gill, E., Schultheiss, P. J., Goswami, I., & Healy, K. E. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.03.015 · Cited by 31 · see citing works
Ifijen, I. H., Awoyemi, C. T., Lekan, O. K., Aworinde, O. R., Faderin, E., Oluwafunke, O., Akanji, T. F. A., Igboanugo, J. C., Udogu, U., Ogidi, G. O., et al. (2024) · RSC Advances · doi:10.1039/d4ra05732e · Cited by 29 · see citing works
Fluorescence lifetime based bioassays
Meyer‐Almes, F. (2017) · Methods and Applications in Fluorescence · doi:10.1088/2050-6120/aa7c7a · Cited by 29 · see citing works
Ma, Y., Nenkov, M., Chen, Y., & Gaßler, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158352 · Cited by 28 · see citing works
Li, W., Hu, X., Wang, S., Xing, Y., Wang, H., Nie, Y., Liu, T., & Song, K. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.02.136 · Cited by 28 · see citing works
Mechanobiology of Colorectal Cancer
Brás, M. M., Sousa, S. R., Carneiro, F., Radmacher, M., & Granja, P. L. (2022) · Cancers · doi:10.3390/cancers14081945 · Cited by 27 · see citing works
Advances in Bio-Based Polymers for Colorectal Cancer Treatment: Hydrogels and Nanoplatforms
Maspes, A., Pizzetti, F., Rossetti, A., Makvandi, P., Sitia, G., & Rossi, F. (2021) · Gels · doi:10.3390/gels7010006 · Cited by 27 · see citing works
Application Progress of Organoids in Colorectal Cancer
Luo, L., Ma, Y., Zheng, Y., Su, J., & Huang, G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.815067 · Cited by 25 · see citing works
Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside
Bērziņa, S., Harrison, A., Taly, V., & Xiao, W. (2021) · Cancers · doi:10.3390/cancers13164192 · Cited by 24 · see citing works
A Tissue Engineering Approach to Metastatic Colon Cancer
Sarvestani, S. K., DeHaan, R. K., Miller, P. G., Bose, S., Shen, X., Shuler, M. L., & Huang, E. H. (2020) · iScience · doi:10.1016/j.isci.2020.101719 · Cited by 20 · see citing works
The Matrix Reloaded—The Role of the Extracellular Matrix in Cancer
Raskov, H., Gaggar, S., Tajik, A., Orhan, A., & Gögenür, I. (2023) · Cancers · doi:10.3390/cancers15072057 · Cited by 22 · see citing works
Stanciu, S. G., König, K., Song, Y. M., Wolf, L., Charitidis, C. A., Bianchini, P., & Goetz, M. (2023) · Biophysics Reviews · doi:10.1063/5.0133027 · Cited by 21 · see citing works
Distinguishing colorectal adenoma from hyperplastic polyp by WNT2 expression
Wang, B., Wang, X., Tseng, Y., Huang, M., Luo, F., Zhang, J., & Liu, J. (2021) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.23961 · Cited by 18 · see citing works
Doherty, E. L., Krohn, G., Warren, E. C., Patton, A., Whitworth, C. P., Rathod, M., Biehl, A., Aw, W. Y., Freytes, D. O., & Polacheck, W. J. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400192 · Cited by 19 · see citing works
Emerging Biomimetic Materials for Studying Tumor and Immune Cell Behavior
Northcutt, L. A., Suarez‐Arnedo, A., & Rafat, M. (2019) · Annals of Biomedical Engineering · doi:10.1007/s10439-019-02384-0 · Cited by 20 · see citing works
Engineering perfused microvascular networks into microphysiological systems platforms
Andrejecsk, J. W., & Hughes, C. C. W. (2018) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2018.02.002 · Cited by 16 · see citing works
Self-citationFeng, Y., Wang, B., Tian, Y., Chen, H., Liu, Y., Fan, H., Wang, K., & Zhang, C. (2019) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2019.111966 · Cited by 15 · see citing works
Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling
Ahmed, T. (2023) · In vitro models · doi:10.1007/s44164-023-00043-2 · Cited by 14 · see citing works
Zhao, W., Liu, J., Jia, Y., Lei, M., Zhang, S., Xi, P., Ma, Y., Zhang, M., Ma, J., Wang, L., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301586 · Cited by 14 · see citing works
Instructive Hydrogels for Primary Tumor Cell Culture: Current Status and Outlook
Jia, Y., Wei, Z., Zhang, S., Yang, B., & Li, Y. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202102479 · Cited by 13 · see citing works
Scarpellino, G., Genova, T., Quarta, E., Distasi, C., Dionisi, M., Fiorio, A., & Munaron, L. (2022) · Cancers · doi:10.3390/cancers14112743 · Cited by 14 · see citing works
Liu, X., Shu, Y., Zhu, J., Fang, H., Su, Y., Ma, H., Li, B., Xu, J., Cheng, Y. Y., Pan, B., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.139346 · Cited by 14 · see citing works
Li, J., Liu, J., Xia, W., Yang, H., Sha, W., & Chen, H. H. (2024) · Technology in Cancer Research & Treatment · doi:10.1177/15330338231221856 · Cited by 13 · see citing works
Ziegler, M. E., Sorensen, A. M., Banyard, D. A., Sayadi, L. R., Chnari, E., Hatch, M. M. S., Tassey, J., Mirzakhanyan, Y., Gershon, P. D., Hughes, C. C. W., et al. (2022) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000009794 · Cited by 12 · see citing works
Self-citationBreast cancer fibroblasts and cross-talk
Magesh, P., Thankachan, S., Venkatesh, T., & Suresh, P. S. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.07.011 · Cited by 14 · see citing works
Kopyeva, I., Bretherton, R. C., Ayers, J., Yu, M., Grady, W. M., & DeForest, C. A. (2025) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c01632 · Cited by 11 · see citing works
Decellularized tissues as platforms for digestive system cancer models
Seifi, Z., Khazaei, M., Cheraghali, D., & Rezakhani, L. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31589 · Cited by 11 · see citing works
Nouri, K., Piryaei, A., Seydi, H., Zarkesh, I., Ghoytasi, I., Shokouhian, B., Najimi, M., & Vosough, M. (2024) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2024.09.003 · Cited by 11 · see citing works
Lü, Y., Xie, H., Zhang, X., Gu, M., Zhang, K., Xia, T., Pan, S. Y., Yin, H., Wu, R. J., You, Y., et al. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111712 · Cited by 11 · see citing works
RUNX Family in Hypoxic Microenvironment and Angiogenesis in Cancers
Lee, Y. M. (2022) · Cells · doi:10.3390/cells11193098 · Cited by 11 · see citing works
Zhou, G., Lin, X., Li, W., Li, H., Zhang, Q., Ding, X., & Sun, W. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.151138 · Cited by 10 · see citing works
Decellularized Tumor Tissues Integrated with Polydopamine for Wound Healing
Li, H., Lin, X., Rao, S., Zhou, G., Meng, L., Yu, Y., Wang, J., Chen, X., & Sun, W. (2024) · Research · doi:10.34133/research.0445 · Cited by 10 · see citing works
Karkanrood, M. V., Tabrizi, M. H., Ardalan, T., Soltani, M., Khadem, F., Nosrat, T., & Moeini, S. (2022) · Inorganic and Nano-Metal Chemistry · doi:10.1080/24701556.2022.2034008 · Cited by 10 · see citing works
Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types
Rathee, M., Umar, S. M., Dev, A. J. R., Kashyap, A., Mathur, S. R., Gogia, A., Mohapatra, P., & Prasad, C. P. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09694-0 · Cited by 10 · see citing works
Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research
Hachey, S. J., Gaebler, D., & Hughes, C. C. W. (2023) · Journal of Visualized Experiments · doi:10.3791/65865 · Cited by 10 · see citing works
Self-citationAa, I., Danilova, T. I., Kuznetsova, A. V., Попова, О. П., & Yanushevich, O. O. (2023) · Biomolecules · doi:10.3390/biom13010122 · Cited by 8 · see citing works
Decellularized diseased tissues: current state‐of‐the‐art and future directions
Li, X., Shan, J., Chen, X., Cui, H., Wen, G., & Yu, Y. (2023) · MedComm · doi:10.1002/mco2.399 · Cited by 6 · see citing works
Reconstruction of the human nipple–areolar complex: a tissue engineering approach
Maistriaux, L., Foulon, V., Fievé, L., Xhema, D., Evrard, R., Manon, J., Coyette, M., Bouzin, C., Poumay, Y., Gianello, P., et al. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1295075 · Cited by 7 · see citing works
3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug Screening
Li, Y., Yan, X., Liu, W., Zhou, L., You, Z., & Du, Y. (2017) · Journal of Visualized Experiments · doi:10.3791/55982 · Cited by 7 · see citing works
Franchi, M., Karamanos, K.-A., Cappadone, C., Calonghi, N., Greco, N., Franchi, L., Onisto, M., & Masola, V. (2022) · Biomolecules · doi:10.3390/biom12121786 · Cited by 7 · see citing works
Torkashvand, M., Rezakhani, L., Habibi, Z., Mikaeili, A., & Rahmati, S. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1502155 · Cited by 6 · see citing works
Hanitrarimalala, V., Prgomet, Z., Hedhammar, M., Tassidis, H., & Wingren, A. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1545017 · Cited by 7 · see citing works
Scaffolds Mimicking the Tumor Microenvironment for In Vitro Malignancy Models
Rosellini, E., & Cascone, M. G. (2025) · Biomimetics · doi:10.3390/biomimetics10100695 · Cited by 5 · see citing works
He, K., Gong, G., Liang, E., Lv, Y., Lin, S., & Xu, J. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101844 · Cited by 5 · see citing works
Nissen, P., Popova, N. V., Gocke, A., Smit, D. J., Wong, G. Y. M., McKay, M. J., Hugh, T. J., David, K. A., Juhl, H. H., Voß, H., et al. (2025) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2025.101026 · Cited by 4 · see citing works
Phasor analysis of fluorescence lifetime data and its application
Lin, D., Niu, J.-J., Liu, X., Zhang, X. L., Zhang, J., Yu, B., & Qu, J. (2020) · Acta Physica Sinica · doi:10.7498/aps.69.20200554 · Cited by 4 · see citing works
Jones, B. C., Elvassore, N., Coppi, P. D., & Giobbe, G. G. (2022) · doi:10.1002/9783527825820.ch1 · Cited by 4 · see citing works
The dilemma of cancer biomechanics assessment: Living soft matter from a rheological perspective
Ferraro, R., Guido, S., & Sergio, C. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.102888 · Cited by 3 · see citing works
Urbaniec-Stompór, J., Michalak, M., & Godlewski, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25189905 · Cited by 3 · see citing works
Antioxidant Properties of Brown Algae in 3D Model for Colorectal Cancer
Khazaei, M., Seyfi, S., Khazaei, M. R., Bozorgi, A., & Rezakhani, L. (2024) · Cell and Tissue Biology · doi:10.1134/s1990519x23700128 · Cited by 3 · see citing works
Zhang, Q., Liu, H., Zhang, X., Wang, H., Lu, W., & Dai, Z. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115449 · Cited by 2 · see citing works
- Authors
- Romero-López, M., Trinh, A. L., Sobrino, A., Hatch, M. M. S., Keating, M. T., Fimbres, C., Lewis, D. E., Gershon, P. D., Botvinick, E. L., Digman, M., Lowengrub, J. S., & Hughes, C. C. W.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Hughes, Christopher C.W.
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 116
- Pages
- 118-129
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC5226635
- OpenAlex
- W2550719584
- Cited by
- 125
- References
- 64
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 20 · 2023: 15 · 2022: 16 · 2021: 16 · 2020: 14 · 2019: 9 · 2018: 8 · 2017: 11
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 304 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (NIH UH3 TR00048, R01HL60067)
- CCWH (NIH SIG 1S10OD016328)
- PDG (NIH P41-RRO3155)
- MD (NIH EB015890, NIH R01HL085339)
- ELB and MTK
- National Science Foundation (DGE-1144901)
- Chao Family Comprehensive Cancer Center
- National Cancer Institute Center (P30A062203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- extracellular matrix, colon cancer, tumor microenvironment, angiogenesis, liver metastasis, extracellular matrix stiffness, vascular network formation, tumor growth, NADH fluorescence lifetime, glycolysis, endothelial cells, cancer metabolism
- MeSH terms
- Colonic Neoplasms, Extracellular Matrix, Humans, Neovascularization, Pathologic, Tumor Cells, Cultured, Cell Proliferation, 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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review