ABSTRACT

Hepatocyte growth factor (HGF), originally identified as a mitogen for hepatocytes [271, 288], was subsequently shown to be identical to scatter factor (SF) [45, 92, 97], a ligand able to induce epithelial cell dissociation [91]. HGF, produced primarily by mesenchymal cells, is therefore a unique growth factor that elicits multiple cellular responses via its receptor, a tyrosine kinase encoded by the proto-oncogene Met [257, 288]. The main biological processes regulated by HGF are mitogenesis, motility and morphogenesis [389, 394], cell dissociation, migration through the extracellular matrix, acquisition of polarity, and tubule formation [338, 380]. This combination of events, also known as invasive growth, is fundamental during the embryonic development of most epithelial tissues. When inappropriately activated, this genetic program confers invasive ability to normal and neoplastic epithelial cells [271, 407].