Hepatocyte growth factor/scatter factor (HGF/SF), the c-met receptor and the behaviour of epithelial cells

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional protein produced by fibroblasts and other mesenchymal cells and active on epithelial and endothelial cells. The factor shares the basic domain organization of plasminogen and other blood proteases and is produced as a single-chain high molecular weight precursor which is subsequently cleaved to produce a biologically active heterodimer. HGF/SF acts on target cells through binding to a cell surface, high-affinity receptor with tyrosine kinase activity encoded by the c-met proto-oncogene. Transduction of the HGF/SF signal in epithelial cells by the met receptor leads either to: (i) cell dissociation, with loss of adhesion and junctional communication, (ii) cell division or (iii) differentiation and morphogenesis. These responses depend on target cells and culture conditions. There is preliminary evidence for a role for HGF/SF in vivo, suggesting that the factor may be involved in the early stages of embryo development and in liver regeneration. A role in cancer growth or dissemination has been proposed but remains to be clarified.