Over Expression Of Hgf Accelerates Hepatitis B Virus-Induced Liver Carcinogenesis And Hastens The Malignancy Of Hepatocellular Carcinoma

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Genetically modified mouse models play important roles in improving our understanding of HGF/MET signaling in liver development, regeneration and in tumor formation. To evaluate the role of HGF/MET in HBV induced HCC, we generated 1) alb-Cre-Metflox/flox mice which lack of MET expression in the liver; 2) a mouse strain over-expressing human HGF (C3HHGF) to determine if MET is required for HCC development and how HGF accelerates HCC malignancy. We show here that overexpression of human HGF in a C3HHGF mouse model induced spontaneous hepatocellular carcinoma (HCC). Such overexpression also accelerated hepatitis B virus (HBV) surface antigen expression in the liver, which in turn selectively promoted the growth of Met-positive hepatocytes and ultimately led to hepatocellular carcinogenesis. We also demonstrate here that HCC in C3HHGF mice presented gene expression patterns highly associated with malignant human HCC. Molecularly, the HCCs of C3HHGF mice had up-regulated VEGF/HGF signal pathways that can be effectively inhibited by pathway inhibitors. We conclude that C3HHGF mouse model can serve as a good tool for studying human HCC, and we suggest that anti-angiogenic therapeutics can be applied for the treatment of HGF-driven HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1320. doi:1538-7445.AM2012-1320