Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice.

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.