Biologic effect of human hepatocyte growth factor (hHGF), which is now known to be the same protein of scatter factor and tumor cytotoxic factor, on gastric cancer cell lines were examined. hHGF messenger RNA expression was undetectable in human gastric cancer cell lines TMK-1 (poorly differentiated adenocarcinoma) and MKN-28 (well differentiated adenocarcinoma). Human fetal lung fibroblast cell line MRC-5 and human stomach derived fibroblast ST-Fib expressed high levels of hHGF mRNA. hHGF production was also confirmed in the culture media of the fibroblast cell lines by enzyme linked immunosorbent assay. Interestingly, TMK-1, having weak expression of E-cadherin, showed marked scattering on 0.1% collagen gel with hHGF (10 ng/ml). The same scattering activity was also observed with fibroblast conditioned medium or with stomach derived fibroblast ST-Fib co-culture. Contrarily, well differentiated adenocarcinoma cell line MKN-28 maintaining strong E-cadherin expression did not show this morphologic change. The expression of c-met proto-oncogene, which encodes the receptor for hHGF, and the biochemical character of hHGF receptor did not differ significantly between TMK-1 and MKN-28. On the other hand, Western blot analysis using specific antibody to phosphotyrosine revealed a difference in phosphoprotein pattern between the two cell lines. These results indicate that hHGF produced by the stromal fibroblasts has a histologic type-specific morphogenic activity on gastric cancer cells with different expression of E-cadherin in a paracrine manner in vivo and a different post-receptor signal transduction mechanism.

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