Roles of cell surface membrane and nuclear prostaglandin receptors in growth factor production during colon carcinogenesis

细胞表面膜和核前列腺素受体在结肠癌发生过程中生长因子产生中的作用

基本信息

批准号：
13670553
负责人：
OTA Shinichi
金额：
$ 2.24万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670553/
关键词：
colon cancer COX-2 prostaglandin VEGF PPAR 大腸腺腫受容体血管内皮増殖因子 PPARγ マクロファージ

项目摘要

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.

各种研究表明，非甾体类抗炎药 (NSAID) 可以预防结肠癌的形成，然而，这些步骤的机制尚未阐明，而环氧合酶 (COX-2) 已被证明在这一现象中发挥着重要作用。我们利用细胞系研究了COX-2在人胃肿瘤中的定位和可能的作用： 1. COX-2在位于上皮下层的间充质细胞中表达。 2. COX-2 也在位于人增生性胃息肉上皮下层的间充质细胞中表达，但在人胃腺瘤中不表达。 3. 前列腺素 (PG) E 诱导血管内皮生长因子 (VEGF) 表达。人类巨噬细胞通过 EP_2 和 EP_4 前列腺素受体 4. 西卡前列素和伊洛前列素，PGI 的特异性配体。 5. PGJ_2 类似物（PPARγ 的特异性配体），但 PGI_2 类似物（PPARδ 的特异性配体）表现出类似的作用。 6. PPARγ 的配体和 PPARδ 的配体。但 PGE 受体或 PGI 受体的配体不能模拟结肠癌细胞系 VEGF 的产生。 7. 瑞巴派特（一种抗溃疡药物）可抑制膜。巨噬细胞 PG 受体介导而非核受体介导的 VEGF 产生增加。