Influence of hepatocyte growth factor secreted from fibroblasts on the growth and invasion of scirrhous gastric cancer

The objective of this study was to show that hepatocyte growth factor (HGF) and HGF receptor (c-met protein) play an important role in the cancer growth and infiltration in scirrhous gastric cancer. The expression level of c-met protein was examined in 90 cases of advanced gastric cancer using anti-c-met antibody. Co-cultivation of each of four gastric cancer cell lines with gastric fibroblasts was performed using a double chamber method. The expression rate of c-met was 79.5% in type 4 tumors, significantly higher than in other types. The expression rates were 63.6% in undifferentiated-type cancer and 36.3% in differentiated-type cancer. Co-cultivation of undifferentiated-type cancer with fibroblasts showed a significantly higher HGF concentration than fibroblasts cultured alone. The growth in three undifferentiated-type cancers was accelerated by an addition of rhHGF and by co-cultivation with fibroblasts and was inhibited by anti-HGF antibody. Moreover rhHGF stimulated the invasion activity of undifferentiated cancer cell lines. These findings suggested that gastric fibroblasts in scirrhous cancer stimulate tumor growth and invasion through activation of the HGF/c-met system.