TGF-beta1 secreted by gastric fibroblasts up-regulates CD44H expression and stimulates the peritoneal metastatic ability of scirrhous gastric cancer cells.
Gastric fibroblast-derived conditioned medium and TGF-beta1 stimulated the adhesion ability of scirrhous gastric cancer cells to mesothelial cells, but not that of well-differentiated gastric cancer cells. The CD44H expression of scirrhous gastric cancer cells was significantly up-regulated by gastric fibroblast-derived CM and TGF-beta1. The stimulated adhesion ability and CD44H expression was significantly inhibited by anti TGF-beta1 neutralizing antibody. These findings suggested that TGF-beta1 secreted by gastric fibroblasts up-regulated the CD44H expression of scirrhous gastric cancer cells, which resulted in the stimulation of the adhesion ability of scirrhous gastric cancer cells to the mesothelium, and increased the peritoneal dissemination potential. These results might explain one of the reasons why scirrhous gastric carcinomas develop frequent peritoneal dissemination.
Koyama
T
T
First Department of Surgery, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Yashiro
M
M
Inoue
T
T
Nishimura
S
S
Hirakawa-YS Chung
K
K
D002293:Adenocarcinoma, Scirrhous / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D018960:Hyaluronan Receptors; D016212:Transforming Growth Factor beta