An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis

Thomas Reiberger, Yunching Chen, Rakesh R. Ramjiawan, Tai Hato, Christopher Fan, Rekha Samuel, Sylvie Roberge, Peigen Huang, Gregory Y. Lauwers, Andrew X. Zhu, Nabeel Bardeesy, Rakesh K. Jain, Dan G. Duda

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl 4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl 4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl 4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4 a '/a ' Stk3 F/a ' (also known as Mst1 a '/a ' Mst2 F/a '; F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis.

Original languageEnglish (US)
Pages (from-to)1264-1274
Number of pages11
JournalNature Protocols
Issue number8
StatePublished - Aug 25 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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