We evaluated the HGF/Met signaling pathway in endometrial cancer cell lines and assessed the anti-cancer effects of foretinib using <i>in vitro</i> and <i>in vivo</i> experimental models.
Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway; it also triggers NF-κB activation and up-regulates COX-2 gene expression in endometrial cancer cells.
Mig-7 expression was more specific than Met expression, the RTK that binds Scatter factor and is used as a marker of poor progression, in endometrial carcinoma as compared to normal endometrial tissue samples.
The effect of HGF on the invasiveness of 3D cocultured endometrial cancer cells and stromal cells appears to be due to induction of MMP-9 mRNA expression in stromal cells and /or increased activation of MMP-2 and MMP-9 by proteolytic digestion.
To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness.