Roles of VLA-2 and VLA-3 on the formation of peritoneal dissemination in gastric cancer.

To clarify the mechanisms of the metastasis on the peritoneal surface from gastric cancer, a novel ex vivo co-culture system using human greater omentum and a highly metastatic cell line, MKN-45-P was developed. MKN-45-P was established from a gastric cancer cell line of MKN-45 by the progressive growing of the intraperitoneal passages. The differences of the expression of metastasis related genes between MKN-45 and MKN-45-P were examined by RT-PCR. Cancer cells adhered only to the naked area of the submesothelial basement membrane, which was exposed by the shrinkage and exfoliation of mesothelial cells of the omentum. The expressions of integrin alpha 2 and alpha 3 subunits in MKN-45-P were extremely elevated compared to those in MKN-45. Integrin beta 1 subunit expression did not change during the intraperitoneal passages. Anti-beta 1 integrin subunit antibody significantly inhibited the adherent number of MKN-45-P on the omentum. These results indicate that VLA-2 and VLA-3 may have an important role in the formation of the peritoneal dissemination from gastric cancer.