Description
Human Hepatocyte Growth Factor (HGF), also known as scatter factor, is a pleiotropic cytokine that shows homology to the enzymes of the blood coagulation cascade. It stimulates the motility and invasion of several cancer cell types and can induce angiogenesis. Recently HGF was found to be identical to scatter factor, a fibroblast-derived factor promoting the dissociation of epithelial and vascular endothelial cell colonies in monolayer cell cultures by stimulating cell migration. HGF is synthesized as a biologically inactive single chain precursor, which is cleaved by a specific, extracellular serum serine protease to a fully active heterodimer. This mature, biologically active HGF consists of a disulfide-linked alpha-beta heterodimer of the two cleavage products. Previous studies have shown that single chain and heterodimeric HGF are equally active in vitro assay systems due to either production of the serine protease in cell culture or the presence of the ubiquitous protease in serum. All biological responses induced by HGF are elicited by binding to its transmembrane tyrosine kinase receptor, which is encoded by the MET proto-oncogene. After autophosphorylation of the receptor different cytoplasmic effectors are activated that bind to the same multifunctional docking site of the receptor. HGF function is essential for normal development. Knockout studies have demonstrated that both ligand and receptor deficient mice display an embryonic lethal phenotype. Hepatocytes have to be primed before they can fully respond to HGF. This priming requires cytokines as TNF and IL-6. Recent studies have suggested that HGF synergizes with basic FGF in the induction of angiogenesis