Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue
Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue
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DOI：
10.1016/j.humpath.2003.10.025
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发表时间：
2004-04-01
期刊：
影响因子：
3.3
通讯作者：
Sakamoto, C
中科院分区：
文献类型：
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作者：
Tatsuguchi, A;Matsui, K;Sakamoto, C
体外研究表明，环氧合酶-2（考克斯-2）通过刺激血管生成生长因子同时抑制癌细胞系中的细胞凋亡来诱导血管生成。对107例胃癌手术切除标本进行了研究，以确定胃癌组织中考克斯-2表达、血管生成和细胞凋亡之间的关系。采用免疫组化方法检测考克斯-2、血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）和Bcl-2的表达。通过CD 34免疫染色测定微血管密度。TUNEL法检测细胞凋亡。考克斯-2仅在癌细胞中表达46例（43%）。考克斯-2表达与VEGF、PDGF表达显著相关。考克斯-2和VEGF的双重染色显示，这些蛋白的共定位是最常见的癌细胞的前进边缘。考克斯-2和VEGF阳性病例的微血管密度高于考克斯-2和VEGF阴性病例。此外，考克斯-2表达与Bcl-2表达相关。考克斯-2阳性的癌细胞凋亡指数低于考克斯-2阴性的病例。多因素分析显示，考克斯-2和VEGF的共表达、年龄、淋巴结状态和浆膜浸润是影响胃癌患者总生存率的独立预后因素。因此，这些数据表明，考克斯-2通过促进血管生成和抑制细胞凋亡参与胃癌的发展。(C)2004年爱思唯尔公司All rights reserved.
In vitro studies suggest that cyclooxyenase-2 (COX-2) induces,9 angiogenesis by stimulating angiogenic growth factors while inhibiting apoptosis in cancer cell lines. A series of 107 gastric adenocarcinoma cases that had undergone gastrectomy was studied to determine the correlation between COX-2 expression, angiogenesis, and apoptosis in human gastric cancer tissue. COX-2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and Bcl-2 were stained by single and dual immunoassaying methods. Microvessel density was determined by immunostaining for CD34. Apoptosis was evaluated with the TUNEL assay. COX-2 expression was positive exclusively in cancer cells in 46 cases (43%). COX-2 expression significantly correlated with VEGF and PDGF expression. Dual staining for COX-2 and VEGF showed that colocalization of these proteins was most frequent at the advancing edge of cancer cells. Microvessel density was higher in COX-2- and VEGF-positive cases than in COX-2- and VEGF-negative cases. In addition, COX-2 expression correlated with Bcl-2 expression. The apoptotic index was lower in COX-2-positive cancer cells than in COX-2-negative cases. Multivariate analysis revealed that coexpression of COX-2 and VEGF, age, lymph node status, and serosal invasion were independent prognostic factors for overall survival in gastric cancer patients. Therefore, these data suggest that COX-2 contributes to gastric cancer development by promoting angiogenesis and inhibiting apoptosis. (C) 2004 Elsevier Inc. All rights reserved.