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CRC的预后，但死亡率最关键的决定因素是诊断时疾病的远处传播。因此，制定更有效的预防措施以避免转移的发作很重要。与未服用这些药物的患者相比，服用非甾体类抗炎药的结肠癌患者的死亡率明显低得多。环氧合酶（COX）是NSAID的主要靶标，诱导型COX COX-2在胃肠道癌中上调。几份流行病学报告表明，COX-2表达在结肠癌的血源转移中具有重要作用。在本研究中，我们研究了Cox-2活性与Cox-2活性的转移性电位和前列腺素E2对肿瘤细胞粘附对内皮细胞的粘附，siAllyl Lewis抗原的表达，以及在Caco-2细胞中确定糖基转移酶基因的表达COX-2表达低的结肠癌细胞系和CACO-2-COX-2，CACO-2细胞编程为过表达COX-2。与CACO-2相比，CACO-2-COX-2通过SPAN-1的SPAN-1水平升高，并且通过SPAN-1依从性对内皮细胞的依从性提高。用COX-2抑制剂治疗可降低SPAN-1表达和对内皮细胞的粘附。在CACO-2-COX-2或PGE2处理的CACO-2中，B3GAL-T5和ST3GAL III和IV表达增强了。 COX-2抑制剂在CACO-2-COX-2中抑制了这些表达。在形内注射术中，肝转移模型，Caco-2-Cox-2转移至肝脏，而Caco-2则没有。用COX-2抑制剂进行预处理降低了转移势的结果，这表明COX-2与癌细胞与内皮细胞的粘附增强之间的直接联系，并通过加速产生siallyl Lewis抗原来增强肝转移潜能。 COX-2抑制剂可能会抑制转移