2002 Fiscal Year Final Research Report Summary
Roles of cell surface membrane and nuclear prostaglandin receptors in growth factor production during colon carcinogenesis
| Project/Area Number |
13670553
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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 |
Gastroenterology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
OTA Shinichi Saitama Medical School, Medicine, Professor, 医学部, 教授 (30185269)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Kenji Saitama Medical School, Medicine, Professor, 医学部, 教授 (80101088)
ARAI Shin Saitama Medical School, Medicine, Assistant, 医学部, 助手 (20306294)
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| Project Period (FY) |
2001 – 2002
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| Keywords | colon cancer / COX-2 / prostaglandin / VEGF / PPAR |
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| Research Abstract |
Various studies have demonstrated that Non-steroidal anti-inflammatory drugs (NSAIDs) prevent colon cancer formation. However, the mechanisms of these steps have not been elucidated yet while cyclooxygenase (COX-2) has been demonstrated to play an important role in this phenomenon. We investigated the localization of COX-2 in human gastric tumors and possible roles using cell lines. What we found was described below: 1. COX-2 was expressed in mesenchymal cells located at sub-epithelial layer of human colonic adenomas. 2. COX-2 was also expressed in mesenchymal cells located at sub-epithelial layer of human hyperplastic gastric polyps but not in human gastric adenomas. 3. Prostaglandin (PG) E induced vascular endothelial growth factor (VEGF) expression by human macrophages through EP_2 and EP_4 prostaglandin receptors. 4. Cicaprost and iloprost, specific ligands for PGI receptors, also stimulated VEGF production by these cells. 5. A PGJ_2 analogue, a specific ligand for PPARγ, but not a PGI_2 analogue, a specific ligand for PPARδ, showed similar effects. 6. Both a ligand for PPARγ and a ligand for PPARδ but not ligands for PGE receptors or PGI receptors simulated VEGF production by colon cancer cell lines. 7. Rebamipide, an anti-ulcer drug, suppressed membrane PG receptor-mediated but not nuclear receptor-mediated increase of VEGF production by macrophages.
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