HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity

Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion , migration, and trespassing of basement membranes. We show here that in MD A-MD-231 carcinoma cells, these steps are elicited by HGF/SF but not by epi dermal growth factor (EGF). Neither factor substantially alters the product ion or activity of extracellular matrix proteases. HGF/SF, but not EGF, sel ectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitro nectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as throug h reconstituted basement membranes. Inhibition assays using function-blocki ng antibodies show that this phenomenon is mediated by multiple integrins i ncluding beta 1, beta 3, beta 4, and beta 5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest tha t HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.