The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
Open accessAbstract
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver. Cholangiocarcinoma (CCA), in contrast, is characterized by a strong desmoplasia that typically occurs in response to the tumor, suggesting a key role of cancer-associated fibroblasts (CAFs) and fibrosis in its tumor microenvironment (TME). Here, we discuss the functional contributions of myofibroblasts, CAFs, and fibrosis to the development of HCC and CCA in the hepatic PME and TME, focusing on myofibroblast- and extracellular matrix–associated growth factors, fibrosis-associated immunosuppressive pathways, as well as mechanosensitive signaling cascades that are activated by increased tissue stiffness. Better understanding of the role of myofibroblasts in HCC and CCA development and progression may provide the basis to target these cells for tumor prevention or therapy.
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Normal liver tissue has an elastic modulus around several kilo Pascal, whereas fibrosis causes increased tissue rigidity to up to 20 kPa.
“Normal liver tissue has been reported to have an elastic modulus around several kilo Pascal, whereas fibrosis causes increased tissue rigidity to up to 20 kPa (Fig. 5L) (31, 32).”
From Stiffness sensing via Piezo1 enhances macrophage efferocytosis and promotes the resolution of liver fibrosis (2024) · cites this paper as [31]
Section 2.4 describes a stiffer tissue environment associated with extracellular-matrix changes, supporting the qualitative link between fibrosis and rigidity. Section 2.2 reports liver-stiffness measurements in kPa, but neither section gives an elastic modulus of several kPa for normal liver or a fibrotic value of up to 20 kPa. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHepatic fibrosis strongly correlates with hepatocellular carcinoma development, with 80-90% of hepatocellular carcinomas arising in fibrotic or cirrhotic livers.
“Notably, there is a strong correlation between hepatic fibrosis and HCC development with 80–90% of HCCs developing in fibrotic or cirrhotic livers.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [70]
Liver fibrosis often precedes HCC and is a risk factor for HCC in chronic liver disease.
“Moreover, this antibiotic cocktail also reduced liver fibrosis 73, which often precedes HCC and represents a risk factor for HCC development in CLD70.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [70]
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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Jemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 54,708 · see citing works
Global cancer statistics, 2012
Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet‐Tieulent, J., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21262 · Cited by 26,858 · see citing works
Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin
Aziz, J., Shezali, H., Radzi, Z., Yahya, N. A., Abu Kassim, N. H., Czernuszka, J., & Rahman, M. T. (2016) · Skin Pharmacology and Physiology · doi:10.1159/000447017 · Cited by 7,323 · see citing works
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 · see citing works
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979 · see citing works
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,208 · see citing works
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · see citing works
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878 · see citing works
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632 · see citing works
Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Levental, K. R., Yu, H., Kass, L., Lakins, J. N., Egeblad, M., Erler, J. T., Fong, S. F. T., Csiszar, K., Giaccia, A., Weninger, W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.10.027 · Cited by 4,101 · see citing works
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089 · see citing works
Tensional homeostasis and the malignant phenotype
Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart-King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.08.010 · Cited by 3,941 · see citing works
El-Serag, H. B. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1001683 · Cited by 3,529 · see citing works
The Extracellular Matrix: Not Just Pretty Fibrils
Hynes, R. O. (2009) · Science · doi:10.1126/science.1176009 · Cited by 3,527 · see citing works
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170 · 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
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver
Friedman, S. L. (2008) · Physiological Reviews · doi:10.1152/physrev.00013.2007 · Cited by 2,842 · see citing works
Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis
Condeelis, J. S., & Pollard, J. W. (2006) · Cell · doi:10.1016/j.cell.2006.01.007 · Cited by 2,693 · see citing works
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681 · see citing works
Distinct role of macrophages in different tumor microenvironments
Lewis, C. E., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4005 · Cited by 2,225 · see citing works
Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219 · see citing works
Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195 · see citing works
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085 · see citing works
Hepatocellular carcinoma pathogenesis: from genes to environment
Farazi, P. A., & DePinho, R. A. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1934 · Cited by 1,979 · see citing works
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M. (2007) · Science · doi:10.1126/science.1140485 · Cited by 1,955 · see citing works
TLR4 enhances TGF-β signaling and hepatic fibrosis
Seki, E., De Minicis, S., Österreicher, C. H., Kluwe, J., Osawa, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Nature Medicine · doi:10.1038/nm1663 · Cited by 1,942 · see citing works
Self-citationRazumilava, N., & Gores, G. J. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61903-0 · Cited by 1,831 · see citing works
Pathogenesis of Liver Fibrosis
Hernandez-Gea, V., & Friedman, S. L. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130246 · Cited by 1,809 · see citing works
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649 · see citing works
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
Bissell, M. J., & Hines, W. C. (2011) · Nature Medicine · doi:10.1038/nm.2328 · Cited by 1,516 · see citing works
Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., Harrington, K., Williamson, P., Moeendarbary, E., Charras, G., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2756 · Cited by 1,478 · see citing works
CXCL12 (SDF-1)/CXCR4 Pathway in Cancer
Teicher, B. A., & Fricker, S. P. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2329 · Cited by 1,453 · see citing works
Mederacke, I., Hsu, C. C., Troeger, J. S., Huebener, P., Mu, X., Dapito, D. H., Pradere, J.-P., & Schwabe, R. F. (2013) · Nature Communications · doi:10.1038/ncomms3823 · Cited by 1,443 · see citing works
Self-citationBañales, J. M., Cardinale, V., Carpino, G., Marzioni, M., Andersen, J. B., Invernizzi, P., Lind, G. E., Folseraas, T., Forbes, S. J., Fouassier, L., et al. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.51 · Cited by 1,382 · see citing works
Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4
Dapito, D. H., Mencin, A., Gwak, G.-Y., Pradere, J.-P., Jang, M.-K., Mederacke, I., Caviglia, J. M., Khiabanian, H., Adeyemi, A., Bataller, R., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.007 · Cited by 1,346 · see citing works
Self-citationGenetic landscape and biomarkers of hepatocellular carcinoma
Zucman-Rossi, J., Villanueva, A., Nault, J.-C., & Llovet, J. M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.061 · Cited by 1,325 · see citing works
Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma
Ilyas, S. I., & Gores, G. J. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.10.013 · Cited by 1,311 · see citing works
Genomic spectra of biliary tract cancer
Nakamura, H. K., Arai, Y., Totoki, Y., Shirota, T., Elzawahry, A., Kato, M., Hama, N., Hosoda, F., Urushidate, T., Ohashi, S., et al. (2015) · Nature Genetics · doi:10.1038/ng.3375 · Cited by 1,287 · see citing works
Gene expression in fixed tissues and outcome in hepatocellular carcinoma
Hoshida, Y., Villanueva, A., Kobayashi, M., Peix, J., Chiang, D. Y., Camargo, A., Gupta, S., Moore, J., Wrobel, M. J., Lerner, J., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804525 · Cited by 1,286 · see citing works
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.
Leek, R., Lewis, C. E., Whitehouse, R. M., Greenall, M. J., Clarke, J., & Harris, A. L. (1996) · PubMed · Cited by 1,187 · see citing works
Maeda, S., Kamata, H., Luo, J., Leffert, H. L., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2005.04.014 · Cited by 1,165 · see citing works
Hepatic inflammation and fibrosis: Functional links and key pathways
Seki, E., & Schwabe, R. F. (2015) · Hepatology · doi:10.1002/hep.27332 · Cited by 972 · see citing works
Self-citationRisk factors for cholangiocarcinoma
Tyson, G. L., & El‐Serag, H. B. (2011) · Hepatology · doi:10.1002/hep.24351 · Cited by 959 · see citing works
The polarization of immune cells in the tumour environment by TGFβ
Flavell, R. A., Sanjabi, S., Wrzesinski, S. H., & Licona-Limón, P. (2010) · Nature Reviews Immunology · doi:10.1038/nri2808 · Cited by 940 · see citing works
Kuang, D., Zhao, Q., Peng, C., Xu, J., Zhang, J., Wu, C. Y., & Zheng, L. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082173 · Cited by 897 · see citing works
Henderson, N. C., Arnold, T. D., Katamura, Y., Giacomini, M. M., Rodriguez, J. D., McCarty, J. H., Pellicoro, A., Raschperger, E., Betsholtz, C., Ruminski, P. G., et al. (2013) · Nature Medicine · doi:10.1038/nm.3282 · Cited by 866 · see citing works
Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace
Baffy, G., Brunt, E. M., & Caldwell, S. H. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.10.027 · Cited by 856 · see citing works
Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma
Morgan, R. L., Baack, B. N., Smith, B. D., Yartel, A. K., Pitasi, M. A., & Falck-Ytter, Y. T. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-5-201303050-00005 · Cited by 830 · see citing works
Burden of Digestive Diseases in the United States Part III: Liver, Biliary Tract, and Pancreas
Everhart, J. E., & Ruhl, C. E. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.02.038 · Cited by 826 · see citing works
Hoechst, B., Ormandy, L. A., Ballmaier, M., Lehner, F., Krüger, C., Manns, M. P., Greten, T. F., & Korangy, F. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.020 · Cited by 793 · see citing works
Liver Fluke Induces Cholangiocarcinoma
Sripa, B., Kaewkes, S., Sithithaworn, P., Mairiang, E., Laha, T., Smout, M. J., Pairojkul, C., Bhudhisawasdi, V., Tesana, S., Thinkamrop, B., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040201 · Cited by 776 · see citing works
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766 · cited 3× · see citing works
“As such, activated and proliferating HSCs have been shown to switch monocytes from inflammatory to an immunosuppressive and tumor-promoting M2 phenotype, thus allowing immune evasion by developing tumors (53, 75).”
BackgroundNAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis
Ma, C., Kesarwala, A. H., Eggert, T., Medina-Echeverz, J., Kleiner, D. E., Jin, P., Stroncek, D. F., Terabe, M., Kapoor, V., ElGindi, M., et al. (2016) · Nature · doi:10.1038/nature16969 · Cited by 766 · cited 2× · see citing works
“In NAFLD, there is a failure of CD4+ T cell–mediated immunosuppression, mediated by linoleic acid–induced mitochondrial ROS generation and subsequent loss of CD4+ T cells, resulting in increased hepatocarcinogenesis (22).”
BackgroundCell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance
Luedde, T., Kaplowitz, N., & Schwabe, R. F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.018 · Cited by 760 · see citing works
Self-citationClinical diagnosis and staging of cholangiocarcinoma
Blechacz, B. R. A., Komuta, M., Roskams, T., & Gores, G. J. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2011.131 · Cited by 749 · see citing works
Toll-Like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1β in Mice
Miura, K., Kodama, Y., Inokuchi, S., Schnabl, B., Aoyama, T., Ohnishi, H., Olefsky, J. M., Brenner, D. A., & Seki, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.03.052 · Cited by 741 · see citing works
Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver
Lu, L., Li, Y., Kim, S. M., Bossuyt, W., Liu, P., Qiu, Q., Wang, Y., Halder, G. A., Finegold, M. J., Lee, J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911427107 · Cited by 721 · see citing works
Schrader, J., Gordon-Walker, T. T., Aucott, R. L., van Deemter, M., Quaas, A., Walsh, S., Benten, D., Forbes, S. J., Wells, R. G., & Iredale, J. P. (2011) · Hepatology · doi:10.1002/hep.24108 · Cited by 720 · see citing works
Role of the Microenvironment in the Pathogenesis and Treatment of Hepatocellular Carcinoma
Hernández–Gea, V., Toffanin, S., Friedman, S. L., & Llovet, J. M. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.002 · Cited by 718 · see citing works
Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas
Horie, Y., Suzuki, A., Kataoka, E., Sasaki, T., Hamada, K., Sasaki, J., Mizuno, K., Hasegawa, G., Kishimoto, H., Iizuka, M., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20513 · Cited by 699 · see citing works
Jiao, Y., Pawlik, T. M., Anders, R. A., Selaru, F. M., Streppel, M. M., Lucas, D. J., Niknafs, N., Guthrie, V. B., Maitra, A., Argani, P., et al. (2013) · Nature Genetics · doi:10.1038/ng.2813 · Cited by 689 · see citing works
Hoechst, B., Voigtlaender, T., Ormandy, L. A., Gamrekelashvili, J., Zhao, F., Wedemeyer, H. H., Lehner, F., Manns, M. P., Greten, T. F., & Korangy, F. (2009) · Hepatology · doi:10.1002/hep.23054 · Cited by 646 · see citing works
Tumor microenvironment: The role of the tumor stroma in cancer
Li, H., Fan, X., & Houghton, J. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21159 · Cited by 646 · see citing works
Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis
Ding, B.-S., Cao, Z., Lis, R., Nolan, D. J., Guo, P., Simons, M., Penfold, M. E., Shido, K., Rabbany, S. Y., & Rafii, S. (2014) · Nature · doi:10.1038/nature12681 · Cited by 626 · see citing works
Pradere, J.-P., Kluwe, J., De Minicis, S., Jiao, J.-J., Gwak, G.-Y., Dapito, D. H., Jang, M.-K., Guenther, N. D., Mederacke, I., Friedman, R., et al. (2013) · Hepatology · doi:10.1002/hep.26429 · Cited by 613 · see citing works
Self-citationPrimary sclerosing cholangitis
Hirschfield, G. M., Karlsen, T. H., Lindor, K. D., & Adams, D. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60096-3 · Cited by 599 · see citing works
Laklai, H., Miroshnikova, Y. A., Pickup, M. W., Collisson, E. A., Kim, G., Barrett, A., Hill, R. C., Lakins, J. N., Schlaepfer, D. D., Mouw, J. K., et al. (2016) · Nature Medicine · doi:10.1038/nm.4082 · Cited by 598 · see citing works
Deletion of NEMO/IKKγ in Liver Parenchymal Cells Causes Steatohepatitis and Hepatocellular Carcinoma
Luedde, T., Beraza, N., Kotsikoris, V., Loo, G., Nenci, A., Vos, R. D., Roskams, T., Trautwein, C., & Pasparakis, M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.12.016 · Cited by 596 · see citing works
Sia, D., Hoshida, Y., Villanueva, A., Roayaie, S., Ferrer, J., Tabak, B., Peix, J., Solé, M., Tovar, V., Alsinet, C., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.001 · Cited by 575 · see citing works
HCC and angiogenesis: possible targets and future directions
Zhu, A. X., Duda, D. G., Sahani, D. V., & Jain, R. K. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.30 · Cited by 565 · see citing works
Lint, P. V., & Libert, C. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0607338 · Cited by 564 · see citing works
Zhu, X., Zhang, J., Zhuang, P., Zhu, H., Zhang, W., Xiong, Y., Wu, W., Wang, L., Tang, Z., & Sun, H. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.6521 · Cited by 555 · see citing works
An Orphan Receptor Tyrosine Kinase Family Whose Members Serve as Nonintegrin Collagen Receptors
Shrivastava, A., Radziejewski, C. H., Campbell, E. B., Kovac, L., McGlynn, M., RYAN, T. E., Davis, S., Goldfarb, M. P., Glass, D. J., Lemke, G., et al. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80004-0 · Cited by 543 · see citing works
Samuel, M. S., Lopez, J. I., McGhee, E. J., Croft, D. R., Strachan, D., Timpson, P., Munro, J., Schröder, E., Zhou, J., Brunton, V. G., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.008 · Cited by 542 · see citing works
Bipotential Adult Liver Progenitors Are Derived from Chronically Injured Mature Hepatocytes
Tarlow, B. D., Pelz, C., Naugler, W. E., Wakefield, L., Wilson, E. M., Finegold, M. J., & Grompe, M. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.09.008 · Cited by 533 · see citing works
Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice
Singal, A. G., & El-Serag, H. B. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.08.014 · Cited by 530 · see citing works
Cholangiocarcinomas can originate from hepatocytes in mice
Fan, B., Malato, Y., Calvisi, D. F., Naqvi, S., Razumilava, N., Ribback, S., Gores, G. J., Dombrowski, F., Evert, M., Chen, X., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63212 · Cited by 529 · see citing works
Collagen Types in Normal and Cirrhotic Liver
Rojkind, M., Giambrone, M. A., & Biempica, L. (1979) · Gastroenterology · doi:10.1016/s0016-5085(79)80170-5 · Cited by 527 · see citing works
Li, H., Wu, K., Tao, K., Chen, L., Zheng, Q., Lu, X., Liu, J., Shi, L., Liu, C., Wang, G., et al. (2012) · Hepatology · doi:10.1002/hep.25777 · Cited by 496 · see citing works
Chan-on, W., Nairismägi, M., Ong, C. K., Lim, W. K., Dima, S., Pairojkul, C., Lim, K. H., McPherson, J. R., Cutcutache, I., Heng, H. L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2806 · Cited by 495 · see citing works
Worldwide trends in mortality from biliary tract malignancies
Patel, T. C. (2002) · BMC Cancer · doi:10.1186/1471-2407-2-10 · Cited by 491 · see citing works
Sakurai, T., He, G., Matsuzawa, A., Yu, G.-Y., Maeda, S., Hardiman, G., & Karin, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.016 · Cited by 487 · see citing works
Exome sequencing of liver fluke–associated cholangiocarcinoma
Ong, C. K., Subimerb, C., Pairojkul, C., Wongkham, S., Cutcutache, I., Yu, W., McPherson, J. R., Allen, G. E., Ng, C. C. Y., Wong, B. H., et al. (2012) · Nature Genetics · doi:10.1038/ng.2273 · Cited by 486 · see citing works
Robust cellular reprogramming occurs spontaneously during liver regeneration
Yanger, K., Zong, Y., Maggs, L. R., Shapira, S. N., Maddipati, R., Aiello, N. M., Thung, S. N., Wells, R. G., Greenbaum, L. E., & Stanger, B. Z. (2013) · Genes & Development · doi:10.1101/gad.207803.112 · Cited by 484 · see citing works
Ichim, G., Lopez, J., Ahmed, S. U., Muthalagu, N., Giampazolias, E., Delgado, M. E., Haller, M., Riley, J. S., Mason, S. M., Athineos, D., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.018 · Cited by 479 · see citing works
He, G., Dhar, D., Nakagawa, H., Font-Burgada, J., Ogata, H., Jiang, Y., Shalapour, S., Seki, E., Yost, S. E., Jepsen, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.031 · Cited by 474 · see citing works
Integrins as therapeutic targets: lessons and opportunities
Cox, D. M., Brennan, M., & Moran, N. M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3266 · Cited by 456 · see citing works
Epidemiology of cholangiocarcinoma: An update focusing on risk factors
Shin, H., Oh, J., Masuyer, E., et al. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01458.x · Cited by 455 · see citing works
Fibrosis-dependent mechanisms of hepatocarcinogenesis
Zhang, D. Y., & Friedman, S. L. (2012) · Hepatology · doi:10.1002/hep.25670 · Cited by 444 · see citing works
The role of tenascin-C in tissue injury and tumorigenesis
Midwood, K. S., & Orend, G. (2009) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-009-0075-1 · Cited by 434 · see citing works
Masuzaki, R., Tateishi, R., Yoshida, H., Goto, E., Sato, T., Ohki, T., Imamura, J., Goto, T., Kanai, F., Kato, N., et al. (2009) · Hepatology · doi:10.1002/hep.22870 · Cited by 433 · see citing works
Finkin, S., Yuan, D., Stein, I., Taniguchi, K., Weber, A., Unger, K., Browning, J. L., Goossens, N., Nakagawa, S., Gunasekaran, G., et al. (2015) · Nature Immunology · doi:10.1038/ni.3290 · Cited by 433 · see citing works
Capece, D., Fischietti, M., Verzella, D., Gaggiano, A., Cicciarelli, G., Tessitore, A., Zazzeroni, F., & Alesse, E. (2012) · BioMed Research International · doi:10.1155/2013/187204 · Cited by 405 · see citing works
Yoshikawa, D., Ojima, H., Iwasaki, M., Hiraoka, N., Kosuge, T., Kasai, S., Hirohashi, S., & Shibata, T. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6604129 · Cited by 404 · see citing works
Kaposi-Novák, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27236 · Cited by 397 · see citing works
Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression
Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., Ou, G., Wijekoon, A. C., Levental, K. R., Gilbert, P. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3497 · Cited by 396 · see citing works
Zhang, K., Corsa, C. A. S., Ponik, S. M., Prior, J. L., Piwnica-Worms, D. R., Eliceiri, K. W., Keely, P. J., & Longmore, G. D. (2013) · Nature Cell Biology · doi:10.1038/ncb2743 · Cited by 393 · see citing works
A Lymphotoxin-Driven Pathway to Hepatocellular Carcinoma
Haybaeck, J., Zeller, N., Wolf, M. J., Weber, A., Wagner, U., Kurrer, M. O., Bremer, J., Iezzi, G., Graf, R., Clavien, P., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.08.021 · Cited by 381 · see citing works
Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998
Taylor-Robinson, S. D., Toledano, M. B., Arora, S., Keegan, T., Hargreaves, S., Beck, A. J., Khan, S. A., Elliott, P., & Thomas, H. C. (2001) · Gut · doi:10.1136/gut.48.6.816 · Cited by 380 · see citing works
Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters
Naba, A., Clauser, K. R., Lamar, J. M., Carr, S. A., & Hynes, R. O. (2014) · eLife · doi:10.7554/elife.01308 · Cited by 377 · see citing works
Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure
Fernández-Sánchez, M. E., Barbier, S., Whitehead, J., Béalle, G., Michel, A., Latorre-Ossa, H., Rey, C., Fouassier, L., Clapéron, A., Brullé, L., et al. (2015) · Nature · doi:10.1038/nature14329 · Cited by 371 · see citing works
Welzel, T. M., McGlynn, K. A., Hsing, A. W., OʼBrien, T. R., & Pfeiffer, R. M. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj234 · Cited by 371 · see citing works
Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes
Sekiya, S., & Suzuki, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63065 · Cited by 348 · see citing works
Lau, E. Y.-T., Lo, J. H. T., Cheng, B. Y.-L., Ma, M. K. F., Lee, J. M. F., Ng, J. K. Y., Chai, S., Lin, C. H., Tsang, S. Y., Ma, S., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.019 · Cited by 334 · see citing works
The multifaceted role of periostin in tumorigenesis
Ruan, K., Bao, S., & Ouyang, G. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0013-7 · Cited by 326 · see citing works
Qian, M., Utzinger, J., Keiser, J., & Zhou, X. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60313-0 · Cited by 319 · see citing works
Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma
Goyal, L., Muzumdar, M. D., & Zhu, A. X. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2791 · Cited by 307 · see citing works
Links Between Hepatic Fibrosis, Ductular Reaction, and Progenitor Cell Expansion
Williams, M. J., Clouston, A. D., & Forbes, S. J. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.11.034 · Cited by 301 · see citing works
Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice
Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G., & Taub, R. (2000) · Hepatology · doi:10.1002/hep.510310123 · Cited by 298 · see citing works
Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care
Nault, J., Bioulac‐Sage, P., & Zucman‐Rossi, J. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.032 · Cited by 296 · see citing works
Czauderna, P. S., MacKinlay, G. A., Perilongo, G., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.06.102 · Cited by 293 · see citing works
Erkan, M., Reiser–Erkan, C., Michalski, C. W., Deucker, S., Sauliunaite, D., Streit, S., Esposito, I., Friess, H., & Kleeff, J. H. (2009) · Neoplasia · doi:10.1593/neo.81618 · Cited by 291 · see citing works
DDR2 receptor promotes MMP-2–mediated proliferation and invasion by hepatic stellate cells
Olaso, E., Ikeda, K., Eng, F. J., Xu, L.-M., Wang, L., Lin, H. C., & Friedman, S. L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112373 · Cited by 291 · see citing works
Hepatic Stellate Cells Secrete Angiopoietin 1 That Induces Angiogenesis in Liver Fibrosis
Taura, K., Minicis, S. D., Seki, E., Hatano, E., Iwaisako, K., Österreicher, C. H., Kodama, Y., Miura, K., Ikai, I., Üemoto, S., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.065 · Cited by 286 · see citing works
Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2
O'Brien, A. J., Fullerton, J. N., Massey, K. A., Auld, G., Sewell, G. W., Naomi-James, S., Newson, J., Karra, E., Winstanley, A. M., Alazawi, W., et al. (2014) · Nature Medicine · doi:10.1038/nm.3516 · Cited by 286 · see citing works
Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma
Amann, T., Bataille, F., Spruß, T., Mühlbauer, M., Gäbele, E., Schölmerich, J., Kiefer, P., Bosserhoff, A., & Hellerbrand, C. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01087.x · Cited by 277 · see citing works
Baril, P., Gangeswaran, R., Mahon, P. C., Caulee, K., Kocher, H. M., Harada, T., Zhu, M., Kalthoff, H., Crnogorac‐Jurcevic, T., & Lemoine, N. R. (2006) · Oncogene · doi:10.1038/sj.onc.1210009 · Cited by 275 · see citing works
Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma
Horlad, H., Komohara, Y., Okabe, H., Masuda, T., Ohnishi, K., Lei, X., Beppu, T., Baba, H., & Takeya, M. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01614.x · Cited by 274 · see citing works
Isobe, T., Okuyama, T., Toyoda, H., Komurasaki, T., Uchida, D., Takayama, Y., & Hanada, K. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7495 · Cited by 269 · see citing works
Kalathil, S. G., Lugade, A. A., Miller, A., Iyer, R. V., & Thanavala, Y. M. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3381 · Cited by 269 · see citing works
Chen, C., Lee, W., Yang, H., Chang, H., Jen, C., Iloeje, U. H., Su, J., Hsiao, C. K., Wang, L., You, S., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.036 · Cited by 268 · see citing works
Cirrhosis Is Present in Most Patients With Hepatitis B and Hepatocellular Carcinoma
Yang, J. D., Kim, W. R., Coelho, R., Mettler, T. A., Benson, J. T., Sanderson, S. O., Therneau, T. M., Kim, B., & Roberts, L. R. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2010.08.019 · Cited by 267 · see citing works
Caspase-3 Promotes Genetic Instability and Carcinogenesis
Liu, X., He, Y., Li, F., Huang, Q., Kato, T. A., Hall, R. P., & Li, C. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.003 · Cited by 263 · see citing works
WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited.
Boulter, L., Guest, R., Kendall, T., Wilson, D., Wojtacha, D., Robson, A., Ridgway, R., Samuel, K., van Rooijen, N., Barry, S., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76452 · Cited by 261 · see citing works
Periostin expression and epithelial-mesenchymal transition in cancer: a review and an update
Morra, L., & Moch, H. (2011) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-011-1151-5 · Cited by 257 · see citing works
de Veire, S. V., Stalmans, I., Heindryckx, F., Oura, H., Tijeras‐Raballand, A., Schmidt, T., Loges, S., Albrecht, I., Jonckx, B., Vinckier, S., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.039 · Cited by 255 · see citing works
Arihara, F., Mizukoshi, E., Kitahara, M., Takata, Y., Arai, K., Yamashita, T., Nakamoto, Y., & Kaneko, S. (2013) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-013-1447-1 · Cited by 254 · see citing works
Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs
Liu, H., Xue, W., Ge, G., Luo, X., Li, Y., Xiang, H., Ding, X., Tian, P., & Tian, X. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.09.076 · Cited by 243 · see citing works
Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies
Sia, D., Tovar, V., Moeini, A., & Llovet, J. M. (2013) · Oncogene · doi:10.1038/onc.2012.617 · Cited by 236 · see citing works
Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001
West, J., WOOD, H. E., Logan, R. F., Quinn, M. J., & Aithal, G. P. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603127 · Cited by 234 · see citing works
Ding, T., Xu, J., Wang, F., Shi, M., Zhang, Y., Li, S., & Zheng, L. (2008) · Human Pathology · doi:10.1016/j.humpath.2008.08.011 · Cited by 232 · see citing works
Roles of liver fluke infection as risk factor for cholangiocarcinoma
Sithithaworn, P., Yongvanit, P., Duenngai, K., et al. (2014) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.62 · Cited by 231 · see citing works
Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions
Matsumoto, K., & Nakamura, T. (2006) · International Journal of Cancer · doi:10.1002/ijc.21808 · Cited by 228 · see citing works
Takehara, T., Tatsumi, T., Suzuki, T., Rucker, E. B., Hennighausen, L. G., Jinushi, M., Miyagi, T., Kanazawa, Y., & Hayashi, N. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.07.019 · Cited by 223 · see citing works
Coulouarn, C., Corlu, A., Glaise, D., Guénon, I., Thorgeirsson, S. S., & Clément, B. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3317 · Cited by 222 · see citing works
Desmoplastic stroma and cholangiocarcinoma: Clinical implications and therapeutic targeting
Sirica, A. E., & Gores, G. J. (2013) · Hepatology · doi:10.1002/hep.26762 · Cited by 220 · see citing works
Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment
Mu, X., Español‐Suñer, R., Mederacke, I., Affò, S., Manco, R., Sempoux, C. L., Lemaigre, F. P., Adili, A., Yuan, D., Weber, A., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77995 · Cited by 214 · see citing works
Self-citationTherapeutic Effects of Deleting Cancer-Associated Fibroblasts in Cholangiocarcinoma
Mertens, J. C., Fingas, C. D., Christensen, J. D., Smoot, R. L., Bronk, S. F., Werneburg, N. W., Gustafson, M. P., Dietz, A. B., Roberts, L. R., Sirica, A. E., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2130 · Cited by 212 · see citing works
Hypoxia: A Link between Fibrogenesis, Angiogenesis, and Carcinogenesis in Liver Disease
Rosmorduc, O., & Housset, C. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1255355 · Cited by 208 · see citing works
Cancers with Higher Density of Tumor-Associated Macrophages Were Associated with Poor Survival Rates
Jung, K. Y., Cho, S. W., Kim, Y. A., Kim, D., Oh, B., Park, D. J., & Park, Y. J. (2015) · Journal of Pathology and Translational Medicine · doi:10.4132/jptm.2015.06.01 · Cited by 206 · see citing works
Hepatic stellate cells: Partners in crime for liver metastases?
Kang, N., Gores, G. J., & Shah, V. H. (2011) · Hepatology · doi:10.1002/hep.24384 · Cited by 201 · see citing works
Paracrine Hedgehog Signaling in Cancer
Theunissen, J.-W. F., & de Sauvage, F. J. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0756 · Cited by 201 · see citing works
Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells
Yang, L., Wang, Y., Mao, H., Fleig, S. V., Omenetti, A., Brown, K. D., Sicklick, J. K., Li, Y., & Diehl, A. M. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.07.032 · Cited by 200 · see citing works
Hypoxia‐induced increase in the production of extracellular matrix proteins in systemic sclerosis
Distler, J. H. W., Jüngel, A., Pileckytė, M., Zwerina, J., Michel, B. A., Gay, R. E., Kowal‐Bielecka, O., Matucci‐Cerinic, M., Schett, G. A., Marti, H. H., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.23074 · Cited by 193 · see citing works
Proangiogenic Role of Tumor–Activated Hepatic Stellate Cells in Experimental Melanoma Metastasis
Olaso, E., Salado, C., Egilegor, E., Gutierrez, V., Santisteban, A., Sancho‐Bru, P., Friedman, S. L., & Vidal‐Vanaclocha, F. (2003) · Hepatology · doi:10.1053/jhep.2003.50068 · Cited by 190 · see citing works
The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma
Sirica, A. E. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2011.222 · Cited by 189 · see citing works
Clinical role of MMP‐2/TIMP‐2 imbalance in hepatocellular carcinoma
Giannelli, G., Bergamini, C., Marinosci, F., Fransvea, E., Quaranta, M., Lupo, L., Schiraldi, O., & Antonaci, S. (2001) · International Journal of Cancer · doi:10.1002/ijc.1635 · Cited by 187 · see citing works
The fibroblast: Sentinel cell and local immune modulator in tumor tissue
Silzle, T., Randolph, G. J., Kreutz, M. P., & Kunz‐Schughart, L. A. (2003) · International Journal of Cancer · doi:10.1002/ijc.11542 · Cited by 185 · see citing works
Kapanadze, T. G., Gamrekelashvili, J., Ma, C., Chan, C., Zhao, F., Hewitt, S. M., Zender, L., Kapoor, V., Felsher, D. W., Manns, M. P., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.06.010 · Cited by 184 · see citing works
Tenascin-C and integrins in cancer
Yoshida, T., Akatsuka, T., & Imanaka‐Yoshida, K. (2015) · Cell Adhesion & Migration · doi:10.1080/19336918.2015.1008332 · Cited by 180 · see citing works
Ankoma‐Sey, V., Wang, Y., & Dai, Z. (2000) · Hepatology · doi:10.1002/hep.510310122 · Cited by 179 · see citing works
Cadamuro, M., Nardo, G., Indraccolo, S., Dall’Olmo, L., Sambado, L., Moserle, L., Franceschet, I., Colledan, M., Massani, M., Stecca, T., et al. (2013) · Hepatology · doi:10.1002/hep.26384 · Cited by 175 · see citing works
Carloni, V., Luong, T. V., & Rombouts, K. (2014) · Liver International · doi:10.1111/liv.12465 · Cited by 174 · see citing works
Unique phenotype of hepatocellular cancers with exon‐3 mutations in beta‐catenin gene†
Cieply, B. W., Zeng, G., Proverbs-Singh, T. A., Geller, D. A., & Monga, S. P. (2008) · Hepatology · doi:10.1002/hep.22695 · Cited by 174 · see citing works
NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma
Wilson, C. L., Jurk, D., Fullard, N., Banks, P., Page, A., Luli, S., Elsharkawy, A. M., Gieling, R. G., Chakraborty, J. B., Fox, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms7818 · Cited by 171 · see citing works
Moles, A., Murphy, L., Wilson, C. L., Chakraborty, J. B., Fox, C., Park, E. J., Mann, J., Oakley, F., Howarth, R., Brain, J., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2013.12.005 · Cited by 169 · see citing works
Neaud, V., Faouzi, S., Guirouilh‐Barbat, J., Bail, B. L., Balabaud, C. P., Bioulac‐Sage, P., & Rosenbaum, J. (1997) · Hepatology · doi:10.1002/hep.510260612 · Cited by 167 · see citing works
Lee, M., Yang, H., Lu, S., Jen, C., Yeh, S., Liu, C., Chen, P., You, S., Wang, L., Chen, W. J., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.1500 · Cited by 161 · see citing works
Myeloid cells in hepatocellular carcinoma
Wan, S., Kuo, N., Kryczek, I., Zou, W., & Welling, T. H. (2015) · Hepatology · doi:10.1002/hep.27867 · Cited by 158 · see citing works
Thuwajit (2009) · Oncology Reports · doi:10.3892/or_00000309 · Cited by 158 · see citing works
Myofibroblast-derived PDGF-BB promotes hedgehog survival signaling in cholangiocarcinoma cells
Fingas, C. D., Bronk, S. F., Werneburg, N. W., Mott, J. L., Guicciardi, M. E., Cazanave, S. C., Mertens, J. C., Sirica, A. E., & Gores, G. J. (2010) · Hepatology · doi:10.1002/hep.24588 · Cited by 157 · see citing works
Vick, B., Weber, A., Urbanik, T., Maass, T., Teufel, A., Krammer, P. H., Opferman, J. T., Schuchmann, M., Galle, P. R., & Schulze‐Bergkamen, H. (2008) · Hepatology · doi:10.1002/hep.22664 · Cited by 157 · see citing works
Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target
Togo, S., Polanska, U. M., Horimoto, Y., & Orimo, A. (2013) · Cancers · doi:10.3390/cancers5010149 · Cited by 156 · see citing works
Ji, J., Eggert, T., Budhu, A., Forgues, M., Takai, A., Dang, H. T., Ye, Q., Lee, J., Kim, J. H., Greten, T. F., et al. (2015) · Hepatology · doi:10.1002/hep.27822 · Cited by 151 · see citing works
Ju, M., Qiu, S., Fan, J., Xiao, Y., Gao, Q., Zhou, J., Li, Y.-W., & Tang, Z. (2009) · American Journal of Clinical Pathology · doi:10.1309/ajcp86ppbngohnnl · Cited by 150 · see citing works
Utispan, K., Thuwajit, P., Abiko, Y., Charngkaew, K., Paupairoj, A., Chau‐in, S., & Thuwajit, C. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-13 · Cited by 149 · see citing works
Marco, V. D., Calvaruso, V., Ferraro, D., Bavetta, M. G., Cabibbo, G., Conte, E., Cammà, C., Grimaudo, S., Pipitone, R. M., Simone, F., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.036 · Cited by 147 · see citing works
Neaud, V. (1997) · Hepatology · doi:10.1053/jhep.1997.v26.pm0009397985 · Cited by 146 · see citing works
Yoshiji, H., Kuriyama, S., Yoshii, J., Ikenaka, Y., Noguchi, R., Hicklin, D. J., Huber, J., Nakatani, T., Tsujinoue, H., Yanase, K., et al. (2002) · Hepatology · doi:10.1053/jhep.2002.32541 · Cited by 145 · see citing works
Höchst, B., Schildberg, F. A., Sauerborn, P., Gäbel, Y. A., Gevensleben, H., Goltz, D., Heukamp, L. C., Türler, A., Ballmaier, M., Gieseke, F., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.04.033 · Cited by 142 · see citing works
Kim, M. N., Kim, S. U., Kim, B. K., et al. (2015) · Hepatology · doi:10.1002/hep.27735 · Cited by 140 · see citing works
A delicate balance: TGF‐β and the tumor microenvironment
Stover, D. G., Bierie, B., & Moses, H. L. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21149 · Cited by 139 · see citing works
Zhang, D. Y., Goossens, N., Guo, J., Tsai, M., Chou, H.-I., Altunkaynak, C., Sangiovanni, A., Iavarone, M. A., Colombo, M., Kobayashi, M., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309655 · Cited by 129 · see citing works
Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma
Miyamoto, M., Ojima, H., Iwasaki, M., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.199 · Cited by 127 · see citing works
Descriptive Epidemiology of Cholangiocarcinoma and Clonorchiasis in Korea
Shin, H., Oh, J., Lim, M. K., Shin, A., Kong, H., Jung, K., Won, Y., Park, S., Park, S., & Hong, S. (2010) · Journal of Korean Medical Science · doi:10.3346/jkms.2010.25.7.1011 · Cited by 122 · see citing works
Suh, B., Park, S., Shin, D. W., Yun, J. M., Yang, H., Yu, S. J., Shin, C., Kim, J., Ahn, E., Lee, H., et al. (2014) · Hepatology · doi:10.1002/hep.27654 · Cited by 121 · see citing works
Ohira, S., Sasaki, M., Harada, K., Sato, Y., Zen, Y., Isse, K., Kozaka, K., Ishikawa, A., Oda, K., Nimura, Y., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050204 · Cited by 120 · see citing works
Weber, A., Boger, R. J., Vick, B., Urbanik, T., Haybaeck, J., Zoller, S., Teufel, A., Krammer, P. H., Opferman, J. T., Galle, P. R., et al. (2009) · Hepatology · doi:10.1002/hep.23479 · Cited by 120 · see citing works
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Guest, R. V., Boulter, L., Kendall, T. J., Minnis-Lyons, S. E., WALKER, R. E., Wigmore, S. J., Sansom, O. J., & Forbes, S. J. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1911 · Cited by 120 · see citing works
Zhao, W., Zhang, L., Yin, Z., Su, W., Ren, G., Zhou, C., You, J., Fan, J., & Wang, X. (2011) · International Journal of Cancer · doi:10.1002/ijc.25920 · Cited by 115 · see citing works
Morishita, R. (2011) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2011.712 · Cited by 114 · see citing works
Sripa, B., Thinkhamrop, B., Mairiang, E., Laha, T., Kaewkes, S., Sithithaworn, P., Periago, M. V., Bhudhisawasdi, V., Yonglitthipagon, P., Mulvenna, J. P., et al. (2012) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0001654 · Cited by 113 · see citing works
Clapéron, A., Mergey, M., Aoudjehane, L., et al. (2013) · Hepatology · doi:10.1002/hep.26585 · Cited by 111 · see citing works
Utispan, K., Sonongbua, J., Thuwajit, P., et al. (2012) · International Journal of Oncology · doi:10.3892/ijo.2012.1530 · Cited by 111 · see citing works
Zhao, W., Zhang, L., Xu, Y., Zhang, Z., Ren, G., Tang, K., Kuang, P., Zhao, B., Yin, Z., & Wang, X. (2014) · Laboratory Investigation · doi:10.1038/labinvest.2013.139 · Cited by 111 · see citing works
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Okabe, H., Beppu, T., Hayashi, H., Horino, K., Masuda, T., Komori, H., Ishikawa, S., Watanabe, M., Takamori, H., Iyama, K.-I., et al. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0568-4 · Cited by 111 · see citing works
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Overexpression of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma
Torimura, T., Ueno, T., Kin, M., et al. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.01.027 · Cited by 109 · see citing works
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Sargiannidou, I., Zhou, J., & Tuszynski, G. P. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020222600803 · Cited by 106 · see citing works
Lai, K. K. Y., Shang, S., Lohia, N., Booth, G. C., Masse, D. J., Fausto, N., Campbell, J. S., & Beretta, L. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002147 · Cited by 101 · see citing works
Thelen, A., Scholz, A., Weichert, W., et al. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.674 · Cited by 100 · see citing works
Zhang, X., Tan, X., Zeng, G., Missé, A., Singh, S., Kim, Y., Klaunig, J. E., & Monga, S. P. (2010) · Hepatology · doi:10.1002/hep.23747 · Cited by 98 · see citing works
Terada, T., Okada, Y., & Nakanuma, Y. (1996) · Hepatology · doi:10.1002/hep.510230608 · Cited by 98 · see citing works
Mikula, M., Proell, V., Fischer, A. N. M., & Mikulits, W. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20772 · Cited by 96 · see citing works
StreetZ, K. L., Wüstefeld, T., Klein, C., Kallen, K.-J., Tronche, F., Betz, U. A. K., Schütz, G., Manns, M. P., Müller, W., & Trautwein, C. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00901-6 · Cited by 94 · see citing works
Discoidin domain receptor 2 is a critical regulator of epithelial–mesenchymal transition
Walsh, L. A., Nawshad, A., & Medici, D. (2011) · Matrix Biology · doi:10.1016/j.matbio.2011.03.007 · Cited by 94 · see citing works
Prakobwong, S., Yongvanit, P., Hiraku, Y., Pairojkul, C., Sithithaworn, P., Pinlaor, P., & Pinlaor, S. (2010) · International Journal of Cancer · doi:10.1002/ijc.25266 · Cited by 92 · see citing works
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- [158]Toyoda H Komurasaki T Uchida D Takayama Y Isobe T 1995 Epiregulin: a novel epidermal growth factor with mitogenic activity for rat primary hepatocytes J Biol Chem 270 7495 500 7706296
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- Authors
- Affo, S., Yu, L.-X., & Schwabe, R. F.
- Affiliations
- Department of Medicine, Columbia University, New York, NY 10032;
- Columbia University (US)
- Venue
- Annual Review of Pathology: Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2017-01-24
- Volume
- 12
- Issue
- 1
- Pages
- 153-186
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- PMC
- PMC5720358
- OpenAlex
- W2411225414
- Cited by
- 757
- References
- 269
- Citations by year
- 2026: 62 · 2025: 97 · 2024: 96 · 2023: 107 · 2022: 104 · 2021: 94 · 2020: 101 · 2019: 48 · 2018: 36 · 2017: 12
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA190844, R01CA200597)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- cancer-associated fibroblasts, liver fibrosis, hepatocellular carcinoma, cholangiocarcinoma, tumor microenvironment, myofibroblasts, desmoplasia, extracellular matrix, growth factors, immunosuppression, mechanosensitive signaling, tissue stiffness, liver cirrhosis, liver cancer progression
- MeSH terms
- Cancer-Associated Fibroblasts, Animals, Humans, Liver Cirrhosis, Liver Neoplasms, Signal Transduction, Myofibroblasts, Tumor Microenvironment
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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.
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