Adhesion of Gastric Carcinoma Cells to Peritoneum Mediated by α3β1 Integrin (VLA-3)

Abstract

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 β1 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 anti-α3 integrin antibody and to a lesser extent by an anti-α2 integrin antibody. In the peritoneal implantation of NUGC-4 human gastric carcinoma cells in athymic mice, treatment of the cells with anti-α2 or anti-α3 integrin antibody reduced the number of disseminated nodules; suppression by the anti-α3 integrin antibody was stronger than that by the anti-α2 integrin antibody. The cDNAs to human α2 and α3 integrins were introduced into K562 leukemic cells, which were positive for the integrin β1 subunit but negative for the α2 or α3 subunit. The α3 integrin-transfected cells adhered to excised peritoneum and to a monolayer of peritoneal mesothelial cells more firmly than did the α2 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 α3β1 integrin. mRNA for these laminin isoforms was found in mesothelial cells from the diaphragm and parietal peritoneum. These results strongly suggest that α3β1 integrin plays an essential role in mediating the initial attachment of cancer cells to the peritoneum, leading to the formation of peritoneal metastasis.