| Project/Area Number |
13671329
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
MASSAKAZU Yashiro Osaka City University, Graduate School of Medicine, Surgical Oncology, Lecture, 大学院・医学研究科, 講師 (60305638)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | gastric carcinoma / peritoneal dissemination / mesothelial cell / hepatocyte growth factor / 腹膜播種性転移 / 線維芽細胞 / HGF / スキルス胃癌 / 宿主微小環境 / CD44H / TGF-β1 / 高分化型細胞株 / 腹膜転移 / 相互作用 |
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| Research Abstract |
Mesothelial cell monolayers have been reported to prevent infiltration of cancer cells into the peritoneum. In this study, we investigated the effects of peritoneal fibroblasts on peritoneal mesothelial cell morphology. Human gastric cancer (OCUM-2MD3), peritoneal fibroblast (NF-2P) and mesothelial (MS-1) cell lines were established in our laboratory. Histology of the peritoneum was investigated following intraperitoneal inoculation of serum-free conditioned media (SF-CM) from OCUM-2MD3 cells into nude mice. SF-CM from peritoneal fibroblasts was added to monolayer-cultured mesothelial cells, and their morphology was examined by phase-contrast microscopy. This experiment was conducted in the presence and absence of neutralizing antibodies against various factors. Mesothelial cells exposed to fibroblasts proliferation became hemispherical and separated from each other, while unexposed mesothelium remained as a flat monolayer. Cultured-mesothelial cells rounded up or exhibited a fibroblas
… More
t-like shape following the addition of peritoneal fibroblast SF-CM. Anti-hepatocyte growth factor (HGF) neutralizing antibody partly inhibited this effect. HGF produced by peritoneal fibroblasts affect the morphology of mesothelial cells in monolayers so that the resulting environment may become prove to the peritoneal dissemination of cancer cells.
The effect of gastric fibroblasts on the adhesion ability and the adhesion molecules expressions of gastric cancer cells was examined. Gastric fibroblasts and TGF-β1 stimulated the adhesion ability of scirrhous gastric cancer cells to mesothelial cells, but not that of well-differentiated gastric cancer cells. CD44H expression of scirrhous gastric cancer cells was significantly up-regulated by NF-14 and TGF-β1. The stimulated adhesion ability and CD44H expressions were significantly inhibited by anti TGF-β1 neutralizing antibody.
These findings suggested that TGF-β1 from gastric fibroblasts up-regulated the CD44H expressions on 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. Less
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