ADHESION POLYPEPTIDES ARE USEFUL FOR THE PREVENTION OF PERITONEAL DISSEMINATION OF GASTRIC-CANCER

Citation
T. Matsuoka et al., ADHESION POLYPEPTIDES ARE USEFUL FOR THE PREVENTION OF PERITONEAL DISSEMINATION OF GASTRIC-CANCER, Clinical & experimental metastasis, 16(4), 1998, pp. 381-388
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
ISSN journal
0262-0898
Volume
16
Issue
4
Year of publication
1998
Pages
381 - 388
Database
ISI
SICI code
0262-0898(1998)16:4<381:APAUFT>2.0.ZU;2-M
Abstract
We examined the effect of adhesion polypeptides on the adhesion and in vasiveness of gastric cancer cell lines, We previously reported the es tablishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OC UM-2M. Both alpha 2 beta 1 and alpha 3 beta 1 integrin expression was markedly increased on OCUM-2MD3 cells compared,vith OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (E CM) was also significantly higher than that of OCUM-2M cells, The adhe sion polypeptides, YIGSR and RGD, and two RGD derivatives significantl y inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well d ifferentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR a nd RGD peptides also significantly inhibited the invasiveness of OCUM- 2MD3 cells, The survival of nude mice with peritoneal dissemination gi ven YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated,vith RGD was also improv ed, and this effect was increased using the RGD derivatives, poly(CEMA -RGDS) and CM-chitin RGDS. These polypeptides appear to block the bind ing of integrins, which are expressed on OCUM-2MD3 cells, to the subme sothelial ECM, and consequently inhibit peritoneal implantation. The p eritoneal injection of adhesion polypeptides may be a new therapy agai nst the dissemination of scirrhous gastric cancer, and may be useful f or the prevention of dissemination in high-risk patients. (C) 1998 Lip pincott-Raven Publishers.