Top

Journal of Cancer Research and Clinical Oncology

Published in:

01-08-2009 | Review

Experimental models of hepatocellular carcinoma: developments and evolution

Authors: Long Wu, Zhao-You Tang, Yan Li

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2009

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The biological mechanisms of hepatocarcinogenesis and progression are poorly understood. Experimental models of HCC provide valuable tools to evaluate the risk factors, new treatment modalities and biologic characteristics. Under the constant evolution in model design and technology development, new experimental models continue to emerge, including spontaneous models, induced models, viral models, transplantable models, and genetically engineered models. These models are used as tools to investigate basic biological mechanisms of growth and differentiation, oncogene function, and as systems to test new diagnostic and therapeutic approaches. Each model has its own advantages and disadvantages. The progress in HCC model construction and studies are summarized in this review.

Abe K, Kurata T, Yamada K, Okumura H, Shikata T (1988) Establishment and characterization of a woodchuck hepatocellular carcinoma cell line (WH44KA). Jpn J Cancer Res 79:342–349PubMed

Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB (1979) Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282:615–616. doi:10.1038/282615a0 PubMed

Ahuja D, Saenz-Robles MT, Pipas JM (2005) SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene 24:7729–7745. doi:10.1038/sj.onc.1209046 PubMed

Albini A (2008) Tumor microenvironment, a dangerous society leading to cancer metastasis. From mechanisms to therapy and prevention. Cancer Metastasis Rev 27:3–4. doi:10.1007/s10555-007-9102-y PubMed

Ali SH, DeCaprio JA (2001) Cellular transformation by SV40 large T antigen: interaction with host proteins. Semin Cancer Biol 11:15–23. doi:10.1006/scbi.2000.0342 PubMed

Alison MR, Lovell MJ (2005) Liver cancer: the role of stem cells. Cell Prolif 38:407–421. doi:10.1111/j.1365-2184.2005.00354.x PubMed

Armengol C, Tarafa G, Boix L, Solé M, Queralt R, Costa D, Bachs O, Bruix J, Capellá G (2004) Orthotopic implantation of human hepatocellular carcinoma in mice: analysis of tumor progression and establishment of the BCLC-9 cell line. Clin Cancer Res 10:2150–2157. doi:10.1158/1078-0432.CCR-03-1028 PubMed

Babinet C, Farza H, Morello D, Hadchouel M, Pourcel C (1985) Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. Science 230:1160–1163. doi:10.1126/science.3865370 PubMed

Baenes JM, Schoental R (1958) Experimental liver tumours. Br Med Bull 14:165–167

Barnard GF, Erickson SK, Cooper AD (1986) Regulation of lipoprotein receptors on rat hepatomas in vivo. Biochim Biophys Acta 879:301–312PubMed

Barone M, Leo DA, Maiorano E, Panella E, Scavo MP, Castellaneta A, Francavilla D, Francioso A (2007) Role of sex steroid hormones on hepatocellular carcinoma (HCC) development in HBV transgenic mice. Dig Liver Dis 39:A23–A24. doi:10.1016/j.dld.2006.12.082

Benedict WF, Gielen JE, Owens IS, Niwa A, Bebert DW (1973) Aryl hydrocarbon hydroxylase induction in mammalian liver cell culture. IV. Stimulation of the enzyme activity in established cell lines derived from rat or mouse hepatoma and from normal rat liver. Biochem Pharmacol 22:2766–2769. doi:10.1016/0006-2952(73)90138-X PubMed

Bradlaw JA, Casterline JL Jr (1979) Induction of enzyme activity in cell culture: a rapid screen for detection of planar polychlorinated organic compounds. J Assoc Off Anal Chem 62:904–916PubMed

Busch SJ, Barnhart RL, Martin GA, Flanagan MA, Jackson RL (1990) Differential regulation of hepatic triglyceride lipase and 3-hydroxy-3-methylglutaryl-CoA reductase gene expression in a human hepatoma cell line, HepG2. J Biol Chem 265:22474–22479PubMed

Calviello G, Palozza P, Piccioni E, Maggiano N, Frattucci A, Franceschelli P, Bartoli GM (1998) Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis. Int J Cancer 75:699–705. doi:10.1002/(SICI)1097-0215(19980302)75:5<699::AID-IJC7>3.0.CO;2-U PubMed

Carbó N, López-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, Quinn LS, López-Soriano FJ, Argilés JM (2000) Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br J Cancer 83:526–531. doi:10.1054/bjoc.2000.1299 PubMed

Céspedes MV, Casanova I, Parreño M, Mangues R (2006) Mouse models in oncogenesis and cancer therapy. Clin Transl Oncol 8:318–329. doi:10.1007/s12094-006-0177-7 PubMed

Cheo DL, Burns DK, Meira LB, Houle JF, Friedberg EC (1999) Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53−/− mice. Cancer Res 59(4):771–775PubMed

Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL (1985) A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science 230:1157–1160. doi:10.1126/science.3865369 PubMed

Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL (1987) Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci USA 84:6909–6913. doi:10.1073/pnas.84.19.6909 PubMed

Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD (1989) Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145–1156. doi:10.1016/0092-8674(89)90770-8 PubMed

Cougot D, Neuveut C, Buendia MA (2005) HBV induced carcinogenesis. J Clin Virol 34:S75–S78. doi:10.1016/S1386-6532(05)80014-9 PubMed

Damo LA, Snyder PW, Franklin DS (2005) Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration between the pRb and p53 pathways. Mol Carcinog 42:109–120. doi:10.1002/mc.20068 PubMed

Darlington GJ, Bernhard HP, Miller RA, Ruddle FH (1980) Expression of liver phenotypes in cultured mouse hepatoma cells. J Natl Cancer Inst 64:809–819PubMed

Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC (2004) From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics 3:73–81. doi:10.1074/mcp.M300094-MCP200 PubMed

Dragani TA, Manenti G, Farza H, Della Porta G, Tiollais P, Pourcel C (1990) Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis. Carcinogenesis 11:953–956. doi:10.1093/carcin/11.6.953 PubMed

Dubois N, Bennoun M, Allemand I, Molina T, Grimber G, Daudet-Monsac M, Abelanet R, Briand P (1991) Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J Hepatol 13:227–239. doi:10.1016/0168-8278(91)90819-W PubMed

Dunsford HA, Sell S, Chisari FV (1990) Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res 50:3400–3407PubMed

Feo F (2007) Models for liver cancer. In: The cancer handbook. Wiley, NY, pp 1–16

Fogh J, Fogh JM, Orfeo T (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 59:221–226PubMed

Frese KK, Tuveson DA (2007) Maximizing mouse cancer models. Nat Rev Cancer 7:645–658. doi:10.1038/nrc2192 PubMed

Frith CH, Wiley L (1982) Spontaneous hepatocellular neoplasms and hepatic hemangiosarcomas in several strains of mice. Lab Anim Sci 32:157–162PubMed

Futakuchi M, Hirose M, Ogiso T, Kato K, Sano M, Ogawa K, Shirai T (1999) Establishment of an in vivo highly metastatic rat hepatocellular carcinoma model. Jpn J Cancer Res 90:1196–1202PubMed

Gold LS, Slone TH, Manley NB, Bernstein L (1991) Target organs in chronic bioassays of 533 chemical carcinogens. Environ Health Perspect 93:233–246. doi:10.2307/3431194 PubMed

Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci USA 77:7380–7384. doi:10.1073/pnas.77.12.7380 PubMed

Haggerty DF, Young PL, Popják G, Carnes WH (1973) Phenylalanine hydroxylase in cultured hepatoxytes. I. Hormonal control of enzyme levels. J Biol Chem 248:223–232PubMed

Hahn FF, Muggenburg BA, Boecker BB (1996) Hepatic neoplasms from internally deposited 144CeCl3. Toxicol Pathol 24:281–289PubMed

Heffelfinger SC, Hawkins HH, Barrish J, Taylor L, Darlington GJ (1992) SK HEP-1: a human cell line of endothelial origin. In Vitro Cell Dev Biol 28:136–142. doi:10.1007/BF02631017

Hoffman RM (1999) Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs 17:343–359. doi:10.1023/A:1006326203858 PubMed

Hoffman RM (2005) Orthotopic metastatic (MetaMouse) models for discovery and development of novel chemotherapy. Methods Mol Med 111:297–322PubMed

Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T (2004) Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 113:1774–1783PubMed

Jacob JR, Sterczer A, Toshkov IA (2004) Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors. Hepatology 39:1008–1016. doi:10.1002/hep.20106 PubMed

Ji XN, Ye SL, Li Y, Tian B, Chen J, Gao DM, Chen J, Bao WH, Liu YK, Tang ZY (2003) Contributions of lung tissue extracts to invasion and migration of human hepatocellular carcinoma cells with various metastatic potentials. J Cancer Res Clin Oncol 129:556–564. doi:10.1007/s00432-003-0475-1 PubMed

Jiao W, Miyazaki K, Kitajima Y (2002) Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer 86:98–101. doi:10.1038/sj.bjc.6600017 PubMed

Kamegaya Y, Hiasa Y, Zukerberg L, Fowler N, Blackard JT, Lin W, Choe WH, Schmidt EV, Chung RT (2005) Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology 41:660–667. doi:10.1002/hep.20621 PubMed

Kerbel RS (2003) Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2:S134–S139PubMed

Killion JJ, Radinsky R, Fidler IJ (1998–1999) Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metastasis Rev 17:279–284. doi:10.1023/A:1006140513233

Kim CM, Koike K, Saito I, Miyamura T, Jay G (1991) HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–320. doi:10.1038/351317a0 PubMed

Knowles BB, Howe CC, Aden DP, Yeager AE, Korba BE, Cote PJ, Buendia MA, Gerin JL, Tennant BC (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 209:497–499. doi:10.1126/science.6248960 PubMed

Koike K (1995) Hepatitis B virus HBx gene and hepatocarcinogenesis. Intervirology 38:134–142PubMed

Koike K, Moriya K, Iino S, Yotsuyanagi H, Endo Y, Miyamura T, Kurokawa K (1994) High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology 19:810–819PubMed

Koike K, Moriya K, Kimura S (2002) Role of hepatitis C virus in the development of hepatocellular carcinoma: transgenic approach to viral hepatocarcinogenesis. J Gastroenterol Hepatol 17:394–400. doi:10.1046/j.1440-1746.2002.02763.x PubMed

Kramer MG, Hernandez-Alcoceba R, Qian C, Prieto J (2005) Evaluation of hepatocellular carcinoma models for preclinical studies. Drug Discov Today 2:41–49

Kulas DT, Goldstein BJ, Mooney RA (1996) The transmembrane protein-tyrosine phosphatase LAR modulates signaling by multiple receptor tyrosine kinases. J Biol Chem 271:748–754. doi:10.1074/jbc.271.2.748 PubMed

Lee H, Kawaguchi T, Nomura K, Kitagawa T (1987) Establishment and characterization of a diethylnitrosamine-initiated woodchuck hepatocyte cell line. Hepatology 7:937–940. doi:10.1002/hep.1840070524 PubMed

Lee TH, Finegold MJ, Shen RF, DeMayo JL, Woo SL, Butel JS (1990) Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J Virol 64:5939–5947PubMed

Lee JH, Ku JL, Park YJ, Lee KU, Kim WH, Park JG (1999) Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA. World J Gastroenterol 5:289–295PubMed

Leenders MW, Nijkamp MW, Borel Rinkes IH (2008) Mouse models in liver cancer research: A review of current literature. World J Gastroenterol 14:6915–6923. doi:10.3748/wjg.14.6915 PubMed

Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM (2002) Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 122:352–365. doi:10.1053/gast.2002.31001 PubMed

Levrero M (2006) Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene 25:3834–3847. doi:10.1038/sj.onc.1209562 PubMed

Li HF, Ling MY, Xie Y, Xie H (1998) Establishment of a lymph node metastatic model of mouse hepatocellular carcinoma Hca-F cells in C3H/Hej mice. Oncol Res 10:569–573PubMed

Li Y, Tang Y, Ye L, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH (2001) Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol 7:630–636PubMed

Li Y, Tang Y, Ye L, Liu B, Liu K, Chen J, Xue Q (2003) Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol 129:43–51. doi:10.1007/s00432-003-0493-z PubMed

Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, Liu YK, Tang ZY (2004) Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol 130:460–468. doi:10.1007/s00432-004-0564-9 PubMed

Li B, Gu W, Zhang C, Han KQ, Ling CQ (2006a) Growth arrest and apoptosis of the human hepatocellular carcinoma cell line BEL-7402 induced by melittin. Onkologie 29:367–371. doi:10.1159/000094711 PubMed

Li Y, Tang ZY, Tian B, Ye SL, Qin LX, Xue Q, Sun RX (2006b) Serum CYFRA 21–1 level reflects hepatocellular carcinoma metastasis: study in nude mice model and clinical patients. J Cancer Res Clin Oncol 132:515–520. doi:10.1007/s00432-006-0098-4 PubMed

Lin SB, Wu LC, Huang SL, Hsu HL, Hsieh SH, Chi CW, Au LC (2000) In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha. J Hepatol 33:601–608. doi:10.1034/j.1600-0641.2000.033004601.x PubMed

Ling CQ, Li B, Zhang C, Zhu DZ, Huang XQ, Gu W, Li SX (2005) Inhibitory effect of recombinant adenovirus carrying melittin gene on hepatocellular carcinoma. Ann Oncol 16:109–115. doi:10.1093/annonc/mdi019 PubMed

Liu G, McDonnell TJ, Montes de Oca Luna R, Kapoor M, Mims B, El-Naggar AK, Lozano G (2000) High metastatic potential in mice inheriting a targeted p53 missense mutation. Proc Natl Acad Sci USA 97:4174–4179. doi:10.1073/pnas.97.8.4174 PubMed

Llovet JM, Lok A (2008) Hepatitis B virus genotype and mutants: risk factors for hepatocellular carcinoma. J Natl Cancer Inst 100:1121–1123. doi:10.1093/jnci/djn261 PubMed

Lou CY, Feng YM, Qian AR, Li Y, Tang H, Shang P, Chen ZN (2004) Establishment and characterization of human hepatocellular carcinoma cell line FHCC-98. World J Gastroenterol 10:1462–1465PubMed

Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY (2008) CD133 + HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 27:1749–1758. doi:10.1038/sj.onc.1210811 PubMed

MacNab GM, Alexander JJ, Lecatsas G, Bey EM, Urbanowicz JM (1976) Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer 34:509–515PubMed

Marx J (2003) Medicine. Building better mouse models for studying cancer. Science 299:1972–1975. doi:10.1126/science.299.5615.1972 PubMed

McCoy GW (1909) A preliminary report on tumors found in wild rats. J Med Res 21:285–296

McLauchlan J (2000) Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat 7:2–14. doi:10.1046/j.1365-2893.2000.00201.x PubMed

Milich DR, Jones JE, Hughes JL, Maruyama T, Price J, Melhado I, Jirik F (1994) Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice. J Immunol 152:455–466PubMed

Monjardino J, Crawford E (1979) Polypeptide profile of HBSAg excreted by a human hepatoma cell line. Virology 96:652–655. doi:10.1016/0042-6822(79)90123-5 PubMed

Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 4:1065–1067. doi:10.1038/2053 PubMed

Morris HP, Meranze DR (1974) Induction and some characteristics of “Minimal Deviation” and other transplantable rat hepatomas. Recent Results Cancer Res 44:103–114

Murakami H, Sanderson ND, Nagy P, Marino PA, Merlino G, Thorgeirsson SS (1993) Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis. Cancer Res 53:1719–1723PubMed

Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA (2003) Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424:561–565. doi:10.1038/nature01819 PubMed

Newell P, Villanueva A, Friedman SL, Koike K, Llovet JM (2008) Experimental models of hepatocellular carcinoma. J Hepatol 48:858–879. doi:10.1016/j.jhep.2008.01.008 PubMed

Novicki DL, Jirtle RL, Michalopoulos G (1983) Establishment of two rat hepatoma cell strains produced by a carcinogen initiation, phenobarbital promotion protocol. In Vitro 19:191–202. doi:10.1007/BF02618059 PubMed

Ogawa K, Nakanishi H, Takeshita F, Futakuchi M, Asamoto M, Imaida K, Tatematsu M, Shirai T (2001) Establishment of rat hepatocellular carcinoma cell lines with differing metastatic potential in nude mice. Int J Cancer 91:797–802. doi:10.1002/1097-0215(200002)9999:9999<::AID-IJC1140>3.0.CO;2-# PubMed

Ohnishi S, Aoyama H, Shiga J, Itai Y, Moriyama T, Ishikawa T, Sasaki N, Yamamoto K, Koshimizu K, Kaneko S (1988) Establishment of a new cell line from a woodchuck hepatocellular carcinoma. Hepatology 8:104–107. doi:10.1002/hep.1840080121 PubMed

Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B (2004) Infectious agents and cancer: criteria for a causal relation. Semin Cancer Biol 14:453–471. doi:10.1016/j.semcancer.2004.06.009 PubMed

Park JG, Lee JH, Kang MS, Park KJ, Jeon YM, Lee HJ, Kwon HS, Park HS, Yeo KS, Lee KU (1995) Characterization of cell lines established from human hepatocellular carcinoma. Int J Cancer 62:276–282. doi:10.1002/ijc.2910620308 PubMed

Park US, Su JJ, Ban KC, Qin L, Lee EH, Lee YI (2000) Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1. Gene 251:73–80. doi:10.1016/S0378-1119(00)00183-9 PubMed

Pattengale PK, Stewart TA, Leder A, Sinn E, Muller W, Tepler I, Schmidt E, Leder P (1989) Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. Am J Pathol 135:39–61PubMed

Ray RB, Lagging LM, Meyer K, Ray R (1996a) Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype. J Virol 70:4438–4443PubMed

Ray RB, Meyer K, Ray R (1996b) Suppression of apoptotic cell death by hepatitis C virus core protein. Virology 226:176–182. doi:10.1006/viro.1996.0644 PubMed

Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111. doi:10.1038/35102167 PubMed

Ryall J, Rachubinski RA, Nguyen M, Rozen R, Broglie KE, Shore GC (1984) Regulation and expression of carbamyl phosphate synthetase I mRNA in developing rat liver and Morris hepatoma 5123D. J Biol Chem 259:9172–9176PubMed

Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS (1996) Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. Am J Pathol 149:407–428PubMed

Sassier P, Bergeron M (1977) Specific inhibition of cell proliferation in the mouse intestine by an aqueous extract of rabbit small intestine. Cell Tissue Kinet 10:223–231PubMed

Schock D, Kuo SR, Steinburg MF, Bolognino M, Sparks JD, Sparks CE, Smith HC (1996) An auxiliary factor containing a 240-kDa protein complex is involved in apolipoprotein B RNA editing. Proc Natl Acad Sci USA 93:1097–1102. doi:10.1073/pnas.93.3.1097 PubMed

Sell S (2003) Mouse models to study the interaction of risk factors for human liver cancer. Cancer Res 63:7553–7562PubMed

Sell S, Leffert HL (2008) Liver cancer stem cells. J Clin Oncol 26:2800–2805. doi:10.1200/JCO.2007.15.5945 PubMed

Shuldiner AR (1996) Transgenic animals. N Engl J Med 334:653–655. doi:10.1056/NEJM199603073341009 PubMed

Singh M, Kumar V (2003) Transgenic mouse models of hepatitis B virus-associated hepatocellular carcinoma. Rev Med Virol 13:243–253. doi:10.1002/rmv.392 PubMed

Skelly J, Copeland JA, Howard CR, Zuckerman AJ (1979) Hepatitis B surface antigen produced by a human hepatoma cell line. Nature 282:617–618. doi:10.1038/282617a0 PubMed

Slagle BL, Lee TH, Medina D, Finegold MJ, Butel JS (1996) Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene. Mol Carcinog 15:261–269. doi:10.1002/(SICI)1098-2744(199604)15:4<261::AID-MC3>3.0.CO;2-J PubMed

Sun FX, Tang ZY, Liu KD, Xue Q, Gao DM, Yu YQ, Zhou XD, Ma ZC (1996) Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens. J Cancer Res Clin Oncol 122:397–402. doi:10.1007/BF01212878 PubMed

Szabó E, Páska C, Kaposi Novák P, Schaff Z, Kiss A (2004) Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis. Pathol Oncol Res 10:5–11. doi:10.1007/BF02893401 PubMed

Takahashi M, Sato T, Sagawa T, Lu Y, Sato Y, Iyama S, Yamada Y, Fukaura J, Takahashi S, Miyanishi K, Yamashita T, Sasaki K, Kogawa K, Hamada H, Kato J, Niitsu Y (2002) E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor. Mol Ther 5(5Pt1):627–634PubMed

Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793–804. doi:10.2353/ajpath.2007.060929 PubMed

Tamano S, Merlino GT, Ward JM (1994) Rapid development of hepatic tumors in transforming growth factor alpha transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N-nitrosodiethylamine and promoted by phenobarbital. Carcinogenesis 15:1791–1798. doi:10.1093/carcin/15.9.1791 PubMed

Tanaka N, Moriya K, Kiyosawa K, Koike K, Aoyama T (2008) Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: implications for HCV-associated hepatocarcinogenesis. Int J Cancer 122:124–131. doi:10.1002/ijc.23056 PubMed

Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD (2004) A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130:187–196. doi:10.1007/s00432-003-0511-1 PubMed

Tatsumi T, Takehara T, Kanto T, Miyagi T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N (2001) Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. Cancer Res 61:7563–7567PubMed

Tellinghuisen TL, Rice CM (2002) Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol 5:419–427. doi:10.1016/S1369-5274(02)00341-7 PubMed

Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, Xue Q (1999) New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer 81:814–821. doi:10.1038/sj.bjc.6690769 PubMed

Toshkov I, Chisari FV, Bannasch P (1994) Hepatic preneoplasia in hepatitis B virus transgenic mice. Hepatology 20:1162–1172PubMed

Turusov VS (1976) Pathology of tumours in laboratory animals. IARC, Lyon, pp 55–57

Unoura M, Kobayashi K, Fukuoka K, Matsushita F, Morimoto H, Oshima T, Kaneko S, Hattori N, Murakami S, Yoshikawa H (1985) Establishment of a cell line from a woodchuck hepatocellular carcinoma. Hepatology 5:1106–1111. doi:10.1002/hep.1840050608 PubMed

Wang XW, Yuan JH, Zhang RG, Guo LX, Xie Y, Xie H (2001) Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice. World J Gastroenterol 7:345–351PubMed

Wang Y, Cui F, Lv Y, Li C, Xu X, Deng C, Wang D, Sun Y, Hu G, Lang Z, Huang C, Yang X (2004) HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology 39:318–324. doi:10.1002/hep.20076 PubMed

Wen JM, Huang JF, Hu L, Wang WS, Zhang M, Sham JS, Xu JM, Zeng WF, Xie D, Liang LJ, Guan XY (2002) Establishment and characterization of human metastatic hepatocellular carcinoma cell line. Cancer Genet Cytogenet 135:91–95. doi:10.1016/S0165-4608(01)00636-7 PubMed

Yamashita YI, Shimada M, Hasegawa H, Minagawa R, Rikimaru T, Hamatsu T, Tanaka S, Shirabe K, Miyazaki JI, Sugimachi K (2001) Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res 61:1005–1012PubMed

Yan J, Yu Y, Wang N, Chang Y, Ying H, Liu W, He J, Li S, Jiang W, Li Y, Liu H, Wang H, Xu Y (2004) LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. Oncogene 23:1939–1949. doi:10.1038/sj.onc.1207306 PubMed

Yoshino H, Futakuchi M, Cho YM, Ogawa K, Takeshita F, Imai N, Tamano S, Shirai T (2005) Modification of an in vivo lung metastasis model of hepatocellular carcinomaby low dose N-nitrosomorpholine and diethylnitrosamine. Clin Exp Metastasis 22:441–447. doi:10.1007/s10585-005-2807-9 PubMed

Yu DY, Moon HB, Son JK, Jeong S, Yu SL, Yoon H, Han YM, Lee CS, Park JS, Lee CH, Hyun BH, Murakami S, Lee KK (1999) Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein. J Hepatol 31:123–132. doi:10.1016/S0168-8278(99)80172-X PubMed

Zannis VI, Breslow JL, SanGiacomo TR, Aden DP, Knowles BB (1981) Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. Biochemistry 20:7089–7096. doi:10.1021/bi00528a006 PubMed

Zheng Y, Chen WL, Louie SG, Yen TS, Ou JH (2007) Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice. Hepatology 45:16–21. doi:10.1002/hep.21445 PubMed

Title: Experimental models of hepatocellular carcinoma: developments and evolution
Authors: Long Wu
Zhao-You Tang
Yan Li
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0591-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 8/2009

Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications

Down-regulation of ribosomal protein L7A in human osteosarcoma

HIF-1α modulation by topoisomerase inhibitors in non-small cell lung cancer cell lines

Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials