Hepatocyte Growth Factor And Met In Tumour Invasionmetastasis From Mechanisms To Cancer Prevention

Kunio Matsumoto and Toshikazu Nakamura

Key words: c-met, hepatocyte growth factor, HGF-antagonist, scatter factor, tumour angiogenesis, tumour-stromal interaction

Abstract: Hepatocyte growth factor (HGF), a ligand for c-met proto-oncogene product of receptor tyrosine kinase, exhibits powerful motogenic and angiogenic activities. The utilization of the HGF-Met system in cancer cells confers invasive and metastatic potentials. HGF potently enhances dissociation of cells, cell-matrix interaction, extracellular matrix breakdown, invasion, and angiogenesis, all critical events in the metastatic cascade. Tumour-stromal interaction mediated by HGF, aberrant expression of Met, autocrine or mutational activation of Met are tightly associated with carcinogenesis and malignant progression in a wide variety of tumours. Notably, NK4, the four kringle-antagonist for HGF-Met signaling inhibited tumour invasion and metastasis. The possibility has arisen that an HGF-antagonist can serve as a new therapeutic strategy for treatment of cancer patients. In normal tissues, HGF supports dynamic tissue remodeling for regeneration and the clinical application of HGF for treatment of organ failure/fibrosis will be initiated within a few years. These "two-pronged approaches" regarding HGF will lead to tissue repair and perhaps even the prevention of cancer.

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