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 beta1 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-alpha3
integrin antibody and to a lesser extent by an anti-alpha2
integrin antibody. In the peritoneal implantation of NUGC-4 human gastric
carcinoma cells in athymic mice, treatment of the cells with anti-alpha2 or anti-alpha3
integrin antibody reduced the number of disseminated nodules; suppression by the anti-alpha3
integrin antibody was stronger than that by the anti-alpha2
integrin antibody. The cDNAs to human alpha2 and alpha3
integrins were introduced into K562 leukemic cells, which were positive for the
integrin beta1 subunit but negative for the alpha2 or alpha3 subunit. The
alpha3 integrin-transfected cells adhered to excised peritoneum and to a monolayer of peritoneal mesothelial cells more firmly than did the
alpha2 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
alpha3beta1 integrin.
mRNA for these
laminin isoforms was found in mesothelial cells from the diaphragm and parietal peritoneum. These results strongly suggest that
alpha3beta1 integrin plays an essential role in mediating the initial attachment of
cancer cells to the peritoneum, leading to the formation of peritoneal
metastasis.