AUTOCRINE HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-MET SIGNALING INDUCES TRANSFORMATION AND THE INVASIVE METASTASTIC PHENOTYPE IN C127 CELLS/

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effe ctor of cells expressing the Met tyrosine kinase receptor. C127 is a n on-tumorigenic mouse cell line which expresses negligible levels of HG F/SF and Met proteins. In the present report we have generated C127 ce lls which overexpress HGP/SF and/or Met proteins, and have analysed th e effect of HGF/SF-Met signaling in these cells. We show that this sig naling pathway stimulates the growth and invasiveness of C127 cells in vitro and that cells overexpressing both HGF/SF and Met proteins (but neither alone) are phenotypically transformed and highly tumorigenic and metastatic in vivo. Our data unequivocally demonstrates the autocr ine dependency of HGF/SF-Met-induced transformation and metastasis in this system and supports the theory that the inappropriate expression of HGF/SF and Met proteins could play a role in the development and sp read of human tumors. In addition, this system may be useful for ident ifying metastasis-associated genes that are activated by HGF/SF-Met si gnaling.