New insights in hepatocellular carcinoma: From bench to bedside

Annals of Translational Medicine

Volumn 1, Issue 2, 2013, Pages

  Minicis, Samuele De ^a   Marzioni, Marco ^a   Benedetti, Antonio ^a   Svegliati Baroni, Gianluca ^a  

^a UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

Author keywords

Hepatocellular carcinoma; Liver fibrosis; Metabolic syndrome; NAFLD; NASH

Indexed keywords

EID: 85015467225     PISSN: 23055839     EISSN: 23055847     Source Type: Journal    
DOI: 10.3978/j.issn.2305-5839.2013.01.06     Document Type: Review

References (111)

1. Pang RW, Poon RT. From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. Oncology 2007;72:30-44.
2. De Minicis S, Kisseleva T, Francis H, et al. Liver carcinogenesis: Rodent models of hepatocarcinoma and cholangiocarcinoma. Dig Liver Dis 2013;45:450-9.
3. Feng H, Cheng AS, Tsang DP, et al. Cell cyclerelated kinase is a direct androgen receptor-regulated gene that drives ß-catenin/T cell factor-dependent hepatocarcinogenesis. J Clin Invest 2011;121:3159-75.
4. Koch KS, Maeda S, He G, et al. Targeted deletion of hepatocyte Ikkbeta confers growth advantages. Biochem Biophys Res Commun 2009;380:349-54.
5. Awuah PK, Rhieu BH, Singh S, et al. ß-Catenin loss in hepatocytes promotes hepatocellular cancer after diethylnitrosamine and phenobarbital administration to mice. PLoS One 2012;7:e39771.
6. Kamino H, Yamazaki Y, Saito K, et al. Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors. Int J Oncol 2011;38:1511-20.
7. Wang M, Halasi M, Kabirov K, et al. Combination treatment with bortezomib and thiostrepton is effective against tumor formation in mouse models of DEN/PBinduced liver carcinogenesis. Cell Cycle 2012;11:3370-2.
8. Hulla JE, Chen ZY, Eaton DL. Aflatoxin B1-induced rat hepatic hyperplastic nodules do not exhibit a site-specific mutation within the p53 gene. Cancer Res 1993;53:9-11.
9. McGlynn KA, Hunter K, LeVoyer T, et al. Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. Cancer Res 2003;63:4594-601.
10. Knight B, Yeoh GC, Husk KL, et al. Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. J Exp Med 2000;192:1809-18.
11. Nakano T, Cheng YF, Lai CY, et al. Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats. J Hepatol 2011;55:415-25.
12. de Lima VM, Oliveira CP, Alves VA, et al. A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. J Hepatol 2008;49:1055-61.
13. Guest I, Ilic Z, Sell S. Age dependence of oval cell responses and bile duct carcinomas in male fischer 344 rats fed a cyclic choline-deficient, ethionine-supplemented diet. Hepatology 2010;52:1750-7.
14. Zhong B, Zhou Q, Toivola DM, et al. Organ-specific stress induces mouse pancreatic keratin overexpression in association with NF-kappaB activation. J Cell Sci 2004;117:1709-19.
15. Kodama Y, Kisseleva T, Iwaisako K, et al. c-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice. Gastroenterology 2009;137:1467-1477.e5.
16. Newell P, Villanueva A, Friedman SL, et al. Experimental models of hepatocellular carcinoma. J Hepatol 2008;48:858-79.
17. Sun FX, Tang ZY, Lui KD, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer 1996;66:239-43.
18. Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer 2007;7:645-58.
19. Tuveson DA, Jacks T. Technologically advanced cancer modeling in mice. Curr Opin Genet Dev 2002;12:105-10.
20. Xiong J, Yao YC, Zi XY, et al. Expression of hepatitis B virus X protein in transgenic mice. World J Gastroenterol 2003;9:112-6.
21. Naas T, Ghorbani M, Alvarez-Maya I, et al. Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2. J Gen Virol 2005;86:2185-96.
22. Nilsson JA, Cleveland JL. Myc pathways provoking cell suicide and cancer. Oncogene 2003;22:9007-21.
23. Lee JS, Chu IS, Mikaelyan A, et al. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet 2004;36:1306-11.
24. Laurent-Puig P, Zucman-Rossi J. Genetics of hepatocellular tumors. Oncogene 2006;25:3778-86.
25. Baek HJ, Lim SC, Kitisin K, et al. Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology 2008;48:1128-37.
26. Nicholes K, Guillet S, Tomlinson E, et al. A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice. Am J Pathol 2002;160:2295-307.
27. Geller SA, Nichols WS, Kim S, et al. Hepatocarcinogenesis is the sequel to hepatitis in Z#2 alpha 1-antitrypsin transgenic mice: histopathological and DNA ploidy studies. Hepatology 1994;19:389-97.
28. Watanabe S, Horie Y, Kataoka E, et al. Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. J Gastroenterol Hepatol 2007;22:S96-S100.
29. Horie Y, Suzuki A, Kataoka E, et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 2004;113:1774-83.
30. Beraza N, Malato Y, Sander LE, et al. Hepatocyte-specific NEMO deletion promotes NK/NKT cell-and TRAILdependent liver damage. J Exp Med 2009;206:1727-37.
31. Luedde T, Beraza N, Kotsikoris V, et al. Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 2007;11:119-32.
32. Seki E, Brenner DA. The role of NF-kappaB in hepatocarcinogenesis: promoter or suppressor? J Hepatol 2007;47:307-9.
33. Inokuchi S, Aoyama T, Miura K, et al. Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis. Proc Natl Acad Sci U S A 2010;107:844-9.
34. Herbst A, Kolligs FT. Wnt signaling as a therapeutic target for cancer. Methods Mol Biol 2007;361:63-91.
35. Merle P, Kim M, Herrmann M, et al. Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol 2005;43:854-62.
36. Terris B, Pineau P, Bregeaud L, et al. Close correlation between beta-catenin gene alterations and nuclear accumulation of the protein in human hepatocellular carcinomas. Oncogene 1999;18:6583-8.
37. Devereux TR, Stern MC, Flake GP, et al. CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1. Mol Carcinog 2001;31:68-73.
38. Satoh S, Daigo Y, Furukawa Y, et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet 2000;24:245-50.
39. Clark GJ, Quilliam LA, Hisaka MM, et al. Differential antagonism of Ras biological activity by catalytic and Src homology domains of Ras GTPase activation protein. Proc Natl Acad Sci U S A 1993;90:4887-91.
40. Baba M, Yamamoto R, Iishi H, et al. Ha-ras mutations in N-nitrosomorpholine-induced lesions and inhibition of hepatocarcinogenesis by antisense sequences in rat liver. Int J Cancer 1997;72:815-20.
41. Bai F, Nakanishi Y, Takayama K, et al. Codon 64 of K-ras gene mutation pattern in hepatocellular carcinomas induced by bleomycin and 1-nitropyrene in A/J mice. Teratog Carcinog Mutagen 2003;Suppl 1:161-70.
42. Challen C, Guo K, Collier JD, et al. Infrequent point mutations in codons 12 and 61 of ras oncogenes in human hepatocellular carcinomas. J Hepatol 1992;14:342-6.
43. Morrison DK, Cutler RE. The complexity of Raf-1 regulation. Curr Opin Cell Biol 1997;9:174-9.
44. Jagirdar J, Nonomura A, Patil J, et al. ras oncogene p21 expression in hepatocellular carcinoma. J Exp Pathol 1989;4:37-46.
45. Calvisi DF, Ladu S, Gorden A, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006;130:1117-28.
46. Liao Y, Tang ZY, Liu KD, et al. Apoptosis of human BEL-7402 hepatocellular carcinoma cells released by antisense H-ras DNA--in vitro and in vivo studies. J Cancer Res Clin Oncol 1997;123:25-33.
47. Grisham JW. Interspecies comparison of liver carcinogenesis: implications for cancer risk assessment. Carcinogenesis 1997;18:59-81.
48. Liao Y, Tang ZY, Ye SL, et al. Modulation of apoptosis, tumorigenesity and metastatic potential with antisense H-ras oligodeoxynucleotides in a high metastatic tumor model of hepatoma: LCI-D20. Hepatogastroenterology 2000;47:365-70.
49. Yoshikawa H, Matsubara K, Qian GS, et al. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet 2001;28:29-35.
50. Wormald S, Hilton DJ. Inhibitors of cytokine signal transduction. J Biol Chem 2004;279:821-4.
51. Nagai H, Kim YS, Konishi N, et al. Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas. Cancer Lett 2002;186:59-65.
52. Yasuda E, Kumada T, Takai S, et al. Attenuated phosphorylation of heat shock protein 27 correlates with tumor progression in patients with hepatocellular carcinoma. Biochem Biophys Res Commun 2005;337:337-42.
53. Budhu A, Forgues M, Ye QH, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 2006;10:99-111.
54. Huang X, Yu C, Jin C, et al. Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes accelerates hepatocarcinogenesis by driving proliferation and vascular endothelial growth factor-induced angiogenesis. Cancer Res 2006;66:1481-90.
55. Schiffer E, Housset C, Cacheux W, et al. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology 2005;41:307-14.
56. Breitkopf K, Haas S, Wiercinska E, et al. Anti-TGFbeta strategies for the treatment of chronic liver disease. Alcohol Clin Exp Res 2005;29:121S-131S.
57. Schulze-Bergkamen H, Fleischer B, Schuchmann M, et al. Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. BMC Cancer 2006;6:232.
58. de Lope CR, Tremosini S, Forner A, et al. Management of HCC. J Hepatol 2012;56:S75-87.
59. Arii S, Tanaka S, Mitsunori Y, et al. Surgical strategies for hepatocellular carcinoma with special reference to anatomical hepatic resection and intraoperative contrastenhanced ultrasonography. Oncology 2010;78:125-30.
60. Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38:200-7.
61. Ishizawa T, Hasegawa K, Aoki T, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008;134:1908-16.
62. Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 2010;252:903-12.
63. Cillo U, Vitale A, Bassanello M, et al. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann Surg 2004;239:150-9.
64. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009;10:35-43.
65. Bargellini I, Sacco R, Bozzi E, et al. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study. Eur J Radiol 2012;81:1173-8.
66. Livraghi T, Meloni F, Di Stasi M, et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 2008;47:82-9.
67. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-9.
68. Malagari K, Alexopoulou E, Chatzimichail K, et al. Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead. Abdom Imaging 2008;33:512-9.
69. Paleri V, Carding P, Chatterjee S, et al. Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study. Head Neck 2012;34:1747-52.
70. Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2.
71. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
72. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34.
73. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997;276:60-6.
74. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003;3:895-902.
75. Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105-11.
76. Hemmati HD, Nakano I, LazareffJA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 2003;100:15178-83.
77. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63:5821-8.
78. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396-401.
79. Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005;65:10946-51.
80. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100:3983-8.
81. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645-8.
82. Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science 2004;306:1568-71.
83. O'Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106-10.
84. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancerinitiating cells. Nature 2007;445:111-5.
85. Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823-35.
86. Chinzei R, Tanaka Y, Shimizu-Saito K, et al. Embryoidbody cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes. Hepatology 2002;36:22-9.
87. Hamazaki T, Iiboshi Y, Oka M, et al. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett 2001;497:15-9.
88. Anjos-Afonso F, Siapati EK, Bonnet D. In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J Cell Sci 2004;117:5655-64.
89. Lee KD, Kuo TK, Whang-Peng J, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004;40:1275-84.
90. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature 2000;406:257.
91. Menthena A, Deb N, Oertel M, et al. Bone marrow progenitors are not the source of expanding oval cells in injured liver. Stem Cells 2004;22:1049-61.
92. Lázaro CA, Rhim JA, Yamada Y, et al. Generation of hepatocytes from oval cell precursors in culture. Cancer Res 1998;58:5514-22.
93. Lowes KN, Brennan BA, Yeoh GC, et al. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol 1999;154:537-41.
94. Spagnoli FM, Amicone L, Tripodi M, et al. Identification of a bipotential precursor cell in hepatic cell lines derived from transgenic mice expressing cyto-Met in the liver. J Cell Biol 1998;143:1101-12.
95. Dumble ML, Croager EJ, Yeoh GC, et al. Generation and characterization of p53 null transformed hepatic progenitor cells: oval cells give rise to hepatocellular carcinoma. Carcinogenesis 2002;23:435-45.
96. Strick-Marchand H, Morosan S, Charneau P, et al. Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes. Proc Natl Acad Sci U S A 2004;101:8360-5.
97. Parent R, Marion MJ, Furio L, et al. Origin and characterization of a human bipotent liver progenitor cell line. Gastroenterology 2004;126:1147-56.
98. Sahin MB, Schwartz RE, Buckley SM, et al. Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver. Liver Transpl 2008;14:333-45.
99. Hüttenhofer A, Kiefmann M, Meier-Ewert S, et al. RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse. EMBO J 2001;20:2943-53.
100. Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novel genes coding for small expressed RNAs. Science 2001;294:853-8.
101. Kiss T. Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell 2002;109:145-8.
102. Kato M, Slack FJ. microRNAs: small molecules with big roles -C. elegans to human cancer. Biol Cell 2008;100:71-81.
103. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-97.
104. Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 2006;25:6188-96.
105. Calin GA, Croce CM. Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest 2007;117:2059-66.
106. He X, He L, Hannon GJ. The guardian's little helper: microRNAs in the p53 tumor suppressor network. Cancer Res 2007;67:11099-101.
107. Iorio MV, Visone R, Di Leva G, et al. MicroRNA signatures in human ovarian cancer. Cancer Res 2007;67:8699-707.
108. Girard M, Jacquemin E, Munnich A, et al. miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol 2008;48:648-56.
109. Gramantieri L, Ferracin M, Fornari F, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently downregulated in human hepatocellular carcinoma. Cancer Res 2007;67:6092-9.
110. Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133:647-58.
111. Jiang J, Gusev Y, Aderca I, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res 2008;14:419-27.