M. Jeffers et al., AUTOCRINE HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-MET SIGNALING INDUCES TRANSFORMATION AND THE INVASIVE METASTASTIC PHENOTYPE IN C127 CELLS/, Oncogene, 13(4), 1996, pp. 853-861
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.