Role of COX-2 in the development of gastric tumor by Helicobacter Pylori

应用免疫组织化学方法检测幽门螺杆菌(Hp)感染前后人胃粘膜组织中COX-2的表达。幽门螺杆菌感染可诱导正常胃粘膜中性粒细胞聚集，但不影响COX-2的表达。在下一步。对胃幽门进行了研究。COX-2在胃增生性息肉表面下的间质细胞中呈强阳性表达。而COX-2在胃腺瘤中仅呈弱阳性表达，微血管密度与COX-2的表达呈正相关。这些结果表明，COX-2与胃增生性息肉的生长有关，而与胃腺瘤的生长无关。由于COX-2主要表达于间充质细胞，因此推测COX-2的产物前列腺素(PGs)促进了肿瘤的生长和进一步的癌变。这一步骤可能是由血管生成介导的。因此，我们研究了PGs对血管内皮细胞生长因子产生的影响。PGS显著增加人巨噬细胞模型U-937细胞的血管内皮生长因子的产生。用基因芯片技术研究这些细胞基因表达的变化。在10,000个基因中，有几个基因在PGs处理后表达增强或降低。每个基因的意义将被研究这一结果表明，在人的胃增生性息肉中，幽门螺杆菌诱导间充质细胞COX-2的表达，促进血管生成、肿瘤的发展和癌症的形成。

Expression of COX-2 in human gastric mucosa with or without Helicobacter Pylori (H.pylori) Infection was immunohistochemically investigated. H.pylori infection induced the accumulation of neutrophils but not COX-2 expression in normal gastric mucosa. In the next step. Gastric pylyps were studied. COX-2 was strongly expressed in mesenchymal cells under the surface of gastric hyperplastic polyps. However, COX-2 was only weekly expressed in gastric adenomas Microvessel density was significantly collated with the expression of COX-2. These results suggest that COX-2 is related to the growth of hyperplastic polyp but not adenoma in stomach.Since COX-2 was mainly expressed in mesenchymal cells, it is postulated that prostaglandins (PGs, product of COX-2) accelerate growth of tumors and further cancer formation. This step may be mediated by angiogenesis. Therefore, we investigated the effect of PGs on VEGF production. PGs dramatically increased VEGF production by U-937 cells, A model of human macrophages. Changes of gene expression was studied by cDNA microarray using these cells. Among 10,000 genes, several of them were increased or decreased after treatment with PGs. Meaning of each gene will be studiedThis results suggest that in human gastric hyperplastic polyp H.pylori induces COX-2 expression in mesenchymal cells and promotes angiogenesis, development of tumor, and cancer formation.