Scatter factor and angiogenesis

Abstract

Scatter factor (hepatocyte growth factor) is a mesenchyme-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. These responses are transduced through the c-met protooncogene product, a transmembrane tyrosine kinase that functions as the SF receptor. SF is a potent angiogenic molecule, and its angiogenic activity is mediated primarily through direct actions on endothelial cells. These include stimulation of cell motility, proliferation, protease production, invasion, and organization into capillary-like tubes. SF is chronically overexpressed in tumors, suggesting that it may function as a tumor angiogenesis factor. SF production in tumors may be due, in part, to an abnormal tumor-stroma interaction, in which the tumor cells secrete factors (SF-IFs) that stimulate SF production by tumor-associated stromal cells. Studies suggest a link between tumor suppressors (antioncogenes) and inhibition of angiogenesis. We hypothesize that tumor suppressor gene mutations may contribute to the activation of an SF-IF-->SF-->c-met pathway, leading to an invasive and angiogenic tumor phenotype. Modulation of this pathway may, ultimately, provide clinically useful methods of enhancing or inhibiting angiogenesis.