RRC ID 1360
Author Takatsuki H, Komatsu S, Sano R, Takada Y, Tsuji T.
Title Adhesion of gastric carcinoma cells to peritoneum mediated by alpha3beta1 integrin (VLA-3).
Journal Cancer Res
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 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.
Volume 64(17)
Pages 6065-70
Published 2004-9-1
DOI 10.1158/0008-5472.CAN-04-0321
PII 64/17/6065
PMID 15342388
MeSH Antibodies / pharmacology Cell Adhesion / physiology Cell Line, Tumor Epithelial Cells / cytology Epithelial Cells / metabolism Humans Integrin alpha2 / biosynthesis Integrin alpha2 / physiology Integrin alpha3 / biosynthesis Integrin alpha3 / physiology Integrin alpha3beta1 / antagonists & inhibitors Integrin alpha3beta1 / immunology Integrin alpha3beta1 / metabolism Integrin alpha3beta1 / physiology* Ligands Peritoneum / pathology* Stomach Neoplasms / pathology*
IF 9.727
Times Cited 56
WOS Category ONCOLOGY
Resource
Human and Animal Cells GT3TKB(RCB0885) MKN1(RCB1003) MKN28(RCB1000)