Role of the adipokine chemerin in hepatocellular carcinoma

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Chemerin is an attractant for immune cells, it regulates angiogenesis and cell proliferation. Our group has shown that active chemerin (Chem-157) induces cell death of hepatoma cells while the viability of primary hepatocytes is not affected. Chem-157 also reduces tumor weight in a HepG2 xenograft mouse model. Further, in the literature reduced expression of liver chemerin in hepatocellular carcinoma (HCC) is found to be associated with poor prognosis. The chemerin receptor CMKLR1 is increased in HCC tissue compared to adjacent non-tumorous tissues. Object of the current study is to evaluate a possible beneficial effect of adenoassociated virus 8 mediated hepatic overexpression of Chem-157 in the diethylnitrosamine mouse model widely used in HCC research. In-vitro studies are performed to identify the underlying signaling pathways involved in Chem-157 induced cell death in human and murine cells. Non-alcoholic steatohepatitis (NASH) is one of the risk factors for HCC development. Hepatic chemerin is increased in NASH liver suggesting that protective function of this protein is lost during progression to HCC. In a NASH-HCC animal model expression of hepatic chemerin and its receptors will be measured to address this issue. Further, chemerin activity is analyzed in serum of HCC and NASH-HCC models. HCC is a frequent cancer worldwide and treatment options for progressed HCC have not been established yet. Preliminary data from our group suggest that Chem-157 selectively kills hepatoma cells and the current project intends to further corroborate these findings.