Emerging Multipotent Aspects of Hepatocyte Growth Factor

Abstract

Specific tissue interactions between epithelia and mesenchyme (or stroma), e.g., epithelial-mesenchymal (or -stromal) interactions mediate crucial aspects of normal development and tissue regeneration. These events affect tissue induction, organogenesis, cell movement, and morphogenesis of multicellular structures. Extensive and diverse studies have established that hepatocyte growth factor (HGF), a ligand for the c-met protooncogene product of receptor tyrosine kinase, is a mesenchymal- or stromal-derived multipotent polypeptide which mediates epithelial-mesenchymal interactions. During embryogenesis, HGF supports organogenesis and morphogenesis of various tissues and organs, including the liver, kidney, lung, gut, mammary gland, tooth, skeletal system, etc. In adult tissues, HGF elicits a potent organotrophic function which supports regeneration of organs including the liver, kidney, and lung. In the brain, HGF is a new member of the family of neurotrophic factors. In neoplastic tissue, HGF is involved in tumor invasion and metastasis, through tumor-stromal interactions. While HGF was originally identified as a potent mitogen for mature hepatocytes, the biological functions of this factor reach far beyond the original identifications. Such being the case, use of HGF for purposes of therapeutics is being given increasing attention.

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease

“…HGF is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. 25,26 Based on our recent finding that HGF exclusively stimulated the growth of endothelial cells without VSMC replication, we further studied the capability of HGF to stimulate angiogenesis as a means of gene therapy.…”

Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium: up-regulation of essential transcription factor for angiogenesis, ets

“…Also HGF is considered a humoral mediator of epithelial-mesenchymal interactions respon-sible for morphogenic tissue interactions during the period of embryonic development and organogenesis. 8,9 Recently, HGF has been reported as a mitogen exclusively for endothelial cells without the replication of vascular smooth muscle cells (VSMC), [10][11][12][13] thereby indicating it as a potential angiogenic growth factor. Indeed, activation of the HGF system promoted angiogenesis in a Matrigel system, 14 however, this system provides far from physiological conditions.…”

Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met

“…HGF is a multipotential modulator of biologic activities in a variety of cell types and it influences the growth, motility, differentiation and morphogenesis of its target cells through the c-Met tyrosine kinase receptor. 9 HGF has been described as a potent chemotactic factor 10 and has been associated with the progression of carcinoma cells. 11 Overexpression of the HGF receptor, c-Met, in malignant cells has been reported in various tissues.…”