Hgf In Cancer Invasion And Metastasis

While HGF exhibits multiple biological activities for remodeling and maintenance of tissues, HGF greatly affects behaviors of a wide variety of cancer cells. Biological activities of HGF

on various types of cancer cells are summarized in Table 1. Consistent with Met receptor expression in normal epithelial cells, HGF targets many types of carcinoma cells (tumour originating from epithelial cells), whereas aberrant expression of the Met receptor has been noted in tumours originating from mesenchymal cells and hematopoetic cells. HGF is involved in malignant behavior of these tumour cells and exhibits distinct biological activities on cancer cells, depending on the cell type. It is noteworthy that HGF has bi-directional effects on proliferation of cancer cells. Consistently, tumor cytotoxic factor, originally identified as fibroblast-derived cytotoxic growth inhibitor for some types of cancer cells, was shown to be identical to HGF (16). Particularly, HGF inhibits proliferation of about 90% of hepatoma cells in vitro, while the number of cancer cells in which HGF induces growth inhibition is lower in other tumour cells (42-44). Bi-directional growth regulation by HGF suggests genetical alteration in intracellular signal transduction pathways from the Met receptor in cancer cells, however, molecular mechanisms responsible for the growth inhibition by HGF are as yet unknown. On the other hand, among the biological activities of HGF on cancer cells, motogenic activity of HGF to stimulate tumour migration and invasion is notable in most tumour cells (Table 1).

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