Hepatocarcinoma cells stimulate hepatocyte growth factor secretion in human liver myofibroblasts

Hepatocellular carcinoma (HCC), the main type of primary liver cancer, is c haracterized by a high rate of intra-hepatic invasion. The stroma of HCC is infiltrated by myofibroblasts. We have previously shown that hepatocyte gr owth factor (HGF) secreted by human liver myofibroblasts greatly increased the in vitro invasiveness of 3 human HCC cell lines. In this study we show that the conditioned medium (CM) from the same HCC cell lines dose-dependen tly stimulates HGF secretion by myofibroblasts. This effect was post-transc riptional as no increase in HGF mRNA was observed. We show that the effect of CM is not due to IL-1, lL-6, IGF-1, bFGF or PDGF, previously shown to st imulate HGF synthesis in other models. Our data demonstrate that HCC cells increase HGF secretion by liver myofibroblasts in a paracrine way that coul d act to enhance invasion.