PMID: 9524767Jan 1, 1997Paper

Met-HGF/SF: tumorigenesis, invasion and metastasis

Ciba Foundation Symposium
George F Vande WoudeJames H Resau

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) is synthesized by mesenchymal cells and is a paracrine effector of cells, predominantly epithelial, that express the Met tyrosine kinase receptor. We have demonstrated that autocrine Met-HGF/SF expression in mouse fibroblasts results in transformation and tumorigenesis. HGF/SF-treated cells expressing Met can respond in a variety of ways: mitogenically, by scattering (motility), and by forming branching tubules in gel matrices (branching morphogenesis). HGF/SF also induces in vitro invasiveness and is angiogenic in in vivo assays. A human cell line and several mouse cell lines that we have constructed to express Met-HGF/SF in an autocrine fashion are tumorigenic, invasive and metastatic in athymic nude mice. Thus, the very complex process of invasion and metastasis can be mediated by a ligand-receptor signalling pathway, and the cell lines we have developed provide important model systems for identifying the signalling molecules that mediate these phenotypes: For example Met-HGF/SF signalling activates the urokinase plasminogen proteolysis network, thus coupling this signal transduction pathway to the proteases that mediate dissolution of the extracellular matrix. Branching morph...Continue Reading

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