Direct and tumor microenvironment mediated influences of 5'-deoxy-5'-(methylthio)adenosine on tumor progression of hepatocellular carcinoma

Introduction: Recently, we have shown that downregulation of methylthioadenosine phosphorylase (MTAP) in hepatocellular carcinoma (HCC) cells is caused by promoter-hypermethylation and induces proliferation and resistance against cytokines. The aim of this study was to expanded this analysis to human HCC tissue und to investigate the molecular mechanisms underlying the tumor-promoting effect of MTAP. Methods and Results: Immunohistochemical analysis of a tissue microarray of 85 human HCCs revealed a significant correlation of MTAP protein expression with advanced tumor stages. Loss of MTAP expression resulted in…