Scatter factor (hepatocyte growth factor) is a potent angiogenesis factor in vivo

Abstract

Scatter factor (SF), a fibroblast-derived cytokine characterized by its ability to convert non-motile epithelial cells to a motile fibroblast-like phenotype, is identical to hepatocyte growth factor (HGF), a broad-spectrum mitogen. SF is a heterodimeric glycoprotein that is homologous to plasminogen and other blood coagulation proteases but lacks proteolytic activity. Its receptor is the c-met proto-oncogene product, a growth factor receptor-like transmembrane tyrosine kinase. This unique cytokine is also synthesized and secreted by vascular smooth muscle cells and acts on endothelial cells to stimulate migration, protease production, invasion, proliferation, and differentiation into capillary-like tubes in vitro. SF-containing implants in mouse subcutaneous tissue and rat cornea induce directed ingrowth of new blood vessels from surrounding tissue, with maximal angiogenic responses at doses of 100-200 ng of SF. Immunoreactive SF is expressed at sites of neovascularization within human psoriatic plaques. These findings suggest that SF may play a significant role in the formation and repair of blood vessels under physiologic and pathologic conditions.