Adhesion of Gastric Carcinoma Cells to Peritoneum Mediated by 3 1 Integrin (VLA-3)

The interaction between gastric carcinoma cells and the peritoneal lining is a key step in peritoneal dissemination. In this study, we examined the roles of the 1 family of integrin receptors in the adhesion of such cells to the peritoneum. The adhesion of several gastric carcinoma cell lines to peritonea excised from mice was inhibited most by an anti3 integrin antibody and to a lesser extent by an anti2 integrin antibody. In the peritoneal implantation of NUGC-4 human gastric carcinoma cells in athymic mice, treatment of the cells with anti2 or anti3 integrin antibody reduced the number of disseminated nodules; suppression by the anti3 integrin antibody was stronger than that by the anti2 integrin antibody. The cDNAs to human 2 and 3 integrins were introduced into K562 leukemic cells, which were positive for the integrin 1 subunit but negative for the 2 or 3 subunit. The 3 integrin-transfected cells adhered to excised peritoneum and to a monolayer of peritoneal mesothelial cells more firmly than did the 2 integrin-transfected cells or the mock transfectant. Reverse transcription-PCR was used to analyze the expression of laminin-5 and laminin-10/11, which have been reported to serve as high-affinity ligands for 3 1 integrin. mRNA for these laminin isoforms was found in mesothelial cells from the diaphragm and parietal peritoneum. These results strongly suggest that 3 1 integrin plays an essential role in mediating the initial attachment of cancer cells to the peritoneum, leading to the formation of peritoneal metastasis.