HGF/SF downstream signaling in human hepatoblastoma and hepatocellular carcinoma cells

Hepatoblastoma (HB) is the most frequently occurring liver cancer in children under 3 years of age. Children with residual disease after initial resection or with HB resistant to chemotherapy have a poor prognosis that is associated with high levels of hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF is a key modulator of many physiological and pathological processes like tissue formation, repair and tumor progression. The final biological outcome of HGF/SF binding to its receptor, c-Met, depends on which pathway is activated. To gain more insight into HGF/SF downstream signaling in HB, we tested various HB cell lines (HepT1, HepT3, HuH6) and a hepatocellular carcinoma (HCC) cell line (HepG2) for activation of various pathways. By immunoblot, immunofluorescence microscopic and EMSA analyses, we observed that HGF/SF has no effect on the Jak/STAT and WNT pathway whereas the Ras/MEK and PI-3K pathways are differently activated. HGF/SF induced cell migration could be inhibited by blocking either of this two pathways clearly showing that HGF/SF induces typical pathways important for tumor progression

* supported by the Swiss National Foundation (SNF)