EVIDENCE FOR A ROLE OF MET-HGF SF DURING RAS-MEDIATED TUMORIGENESIS/METASTASIS/

Aberrations in Met-hepatocyte growth factor/scatter factor (HGF/SF) si gnaling have been implicated in the acquisition of tumorigenic and met astatic phenotypes, Here we show that murine NIH3T3 and C127 cells tra nsformed by the Ras oncogene overexpress the Met receptor, resulting i n enhanced HGF/SF-mediated responses in vitro including invasion throu gh basement membrane. Accompanying the increase in Met in ras-transfor med NIH3T3 cells, there is a decrease in endogenous HGF/SF expression as previously observed in cells exogenously overexpressing Met. Howeve r, subcutaneously grown tumors and experimental lung metastases derive d from these cells express significantly higher levels of endogenous H GF/SF together with high levels of Met, These results suggest Met-HGF/ SF signaling enhances tumor growth and metastasis of Ras-transformed N IH3T3 cells.