Scatter factor (SF) is a pleiotropic growth factor that recently has been shown to induce epithelial cell proliferation, random motility, and invasion via interaction with its receptor, a tyrosine kinase encoded by the c-met proto-oncogene.
Hepatocyte growth factor (HGF) has been revealed to have various functions such as regeneration, cancer invasion and tumor suppression in normal and cancer cells of different organs.
Here we show that murine NIH3T3 and C127 cells transformed by the Ras oncogene overexpress the Met receptor, resulting in enhanced HGF/SF-mediated responses in vitro including invasion through basement membrane.
Inhibition by platelet-activating factor of Src- and hepatocyte growth factor-dependent invasiveness of intestinal and kidney epithelial cells. Phosphatidylinositol 3'-kinase is a critical mediator of tumor invasion.
In addition, decreased placental production of HGF in preeclampsia provides a potential mechanism for the lack of trophoblast invasion that is seen in this pregnancy disorder.
Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro.
We have examined here the properties of NK4, an HGF variant containing the N-terminal hairpin plus the 4 kringle domains, on tumour cell proliferation, dissociation and invasion using human colorectal cancer cells (HT115).
These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion.
We have shown that hepatocyte growth factor, secreted by human liver myofibroblasts, promoted in vitro invasion of human hepatocellular carcinoma cell lines.
These results suggest that HGF plays an important role in invasion and metastasis of oral SCC cells as a paracrine factor, and an elevated HGF level in the cancer tissue can be a predictive marker for metastasis formation in patients with oral SCC.
Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase.
This provides a new mechanism in HGF/SF-induced cell scattering, resulting in a switch to a more invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.
We conclude that in vivo, both autocrine and paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET system are likely to contribute to tumor invasion and angiogenesis.
Furthermore, we have defined a novel pathway for hepatocyte growth factor (HGF)-induced glioma cell migration and invasion which requires the induction of TGF-beta2 expression.
These data define a novel pathway for HGF-induced glioma cell migration and invasion, which requires ezrin, changes in the BCL-2/BAX rheostat, and the induction of TGF-beta(2) expression in vitro, and underscore the important role of HGF signaling in vivo.
Hepatocyte growth factor/scatter factor (HGF/SF), a cytokine associated with cancer cell migration and invasion, is synthesised as pro-HGF/SF and requires activation by factors such as the HGF activator (HGFA).
To disrupt endogenous Met signaling, we constructed dominant-negative mutants of both human and murine Met and showed that these can inhibit HGF/SF-mediated Met signaling and cell invasion of ras-transformed cells in vitro.
We studied the effect of HGF/SF on invasiveness of SKG-IIIa and Hela-S3 in an invasion model of the modified Boyden chamber method and by electron microscopy.
A proposed HGF antagonist, NK4 (an amino-terminal kringle-domain peptide of HGF), inhibits tumor growth/invasion through the competition of HGF binding to its receptor, c-Met, and acts as an angiogenesis inhibitor.