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Cyclooxy genase-2 Activity Altered the Cell-Surface Carbohydrate Antigens on. Colon. Cancer Cells and Enhanced Liver Metastasis

环氧化酶 2 活性改变了细胞表面碳水化合物抗原。

基本信息

批准号：
13670514
负责人：
TSUJII Masahiko
金额：
$ 2.37万
依托单位：
Osaka University
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

项目摘要

Recent advances in surgical treatment have improved the prognosis of CRC, but the most critical determinant of mortality is distant spread of disease at the time of diagnosis. Therefore, it is important to develop more effective prevention measures to avoid the onset of metastasis. The mortality rates from colon cancer patients who are taking nonsteroidal anti-inflammatory drugs are significantly low compared with those who are not taking these drugs. Cyclooxygenase (COX) is a major target of NSAIDs and the inducible COX, COX-2, is upregulated in gastrointestinal cancers. Several epidemiological reports suggested that COX-2 expression has an important role in hematogenous metastasis of colon cancer. In the present study, we investigated the interaction between COX-2 activity and metastatic potentialEffects of COX-2 activity and prostaglandin E2 on tumor cell adhesion to endothelial cells, expression of sialyl Lewis antigens, and glycosyltransferase genes were determined in Caco-2 cells, a colon cancer cell line with low COX-2 expression, and Caco-2-COX-2, Caco-2 cells programmed to overexpress COX-2. Caco-2-COX-2 had increased Span-1 levels and increased adherence to endothelial cells via Span-1 compared with Caco-2. Treatment with COX-2 inhibitors decreased Span-1 expression and adherence to endothelial cells. B3Gal-T5 and ST3Gal III and IV expression were enhanced in Caco-2-COX-2 or PGE2-treated Caco-2. COX-2 inhibitors inhibited these expressions in Caco-2-COX-2. In intra-splenic injection, a model of liver metastasis, Caco-2-COX-2 metastasized to the liver, whereas Caco-2 did not. Pretreatment with COX-2 inhibitors reduced the metastatic potentialThese results indicate a direct link between COX-2 and enhanced adhesion of carcinoma cells to endothelial cells, and enhanced liver metastatic potential via accelerated production of sialyl Lewis antigens. COX-2 inhibitors may suppress metastasis

手术治疗的最新进展改善了结直肠癌的预后，但死亡率的最关键决定因素是在诊断时疾病的远处扩散。因此，制定更有效的预防措施以避免转移的发生是非常重要的。服用非甾体类抗炎药的结肠癌患者的死亡率明显低于不服用这些药物的患者。环氧合酶（COX）是非甾体抗炎药的主要靶点，其诱导型COX COX-2在胃肠道肿瘤中表达上调。一些流行病学报告提示COX-2表达在结肠癌血行转移中起重要作用。在低COX-2表达的结肠癌细胞系Caco-2细胞和高表达COX-2的Caco-2-COX-2细胞中，我们检测了COX-2活性和前列腺素E2对肿瘤细胞粘附内皮细胞、唾液Lewis抗原表达和糖基转移酶基因的影响。与Caco-2相比，Caco-2- cox -2增加了Span-1水平，并通过Span-1增加了对内皮细胞的粘附。COX-2抑制剂降低了Span-1的表达和对内皮细胞的粘附。B3Gal-T5和ST3Gal III和IV在Caco-2- cox -2或pge2处理的Caco-2中表达增强。COX-2抑制剂抑制Caco-2-COX-2的这些表达。在脾内注射肝转移模型中，Caco-2- cox -2转移到肝脏，而Caco-2没有。这些结果表明，COX-2与癌细胞与内皮细胞的粘附增强，以及通过加速唾液Lewis抗原的产生而增强肝转移电位之间存在直接联系。COX-2抑制剂可能抑制转移