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
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.