|Budget Amount *help
¥3,700,000 (Direct Cost : ¥3,700,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1995 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into submucosa of stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth-interaction between gastric cancer cells and fibroblasts was examined. We established a new scirrhous gastric cancer cell line, OCUM-2M,and fibroblast, NF-8, derived from a primary tumor of stomach taken by total gastrectomy. NF-8 specifically stimulated the growth of OCUM-2M cells, but not that of well-differentiated adenocarcinoma cells. The growth factor (s) from gastric fibroblasts, apparent molecular weights of 10,000 dalton, which was distinct from various defined growth factors may play an important role in the progression of scirrhous gastric cancer cells. We then examined the effect of NF-8 on the invasiveness of OCUM-2M.NF-8 stimulated significantly the invasiveness of OCUM-2M.TGF-beta and HGF increased significantly the invasiveness. The stimulating activity of NF-8 was inhi
bited significantly by anti-TGF-b neutralizing antibody or anti-HGF neutralizing antibody. These findings suggested that TGF-b and HGF produced by gastric fibroblasts affected the invasiveness of scirrhous gastric cancer cells. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. We then investigated the mechanisms responsible for peritoneal dissemination. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells, buta not OCUM-2M cells in unde mice. The binding ability of OCUM-2MD3 cells was significantly greater than that of OCUM-2M cells. The binding ability of OCUM-2MD3 cells to mesothelial cells was inhibited in the presence of anti-CD44H monoclonal antibody, but that of OCUM-2M cells was not. The binding and invasive ability of OCUM-2MD3 cells were significantly decreased following the addition of anti-a2b1 and a3b1-integrin antibody. These results suggest that adhesiveness and invasiveness in peritoneal implantation of scirrhous gastric carcinoma might be closely associated with CD44H,alpha2beta1 and alpha3beta1-integrin.