Department of Pathology, Dongguk University College of Medicine, Gyeongju, Korea.
Yonsei Med J. 2009 Dec 31;50(6):818-24. doi: 10.3349/ymj.2009.50.6.818. Epub 2009 Dec 18.
Down-regulation of E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT). EMT progression in cancer cells is associated with the loss of certain epithelial markers and the acquisition of a mesenchymal phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis in colon cancer. This study investigated the relationship between E-cadherin and COX-2 in colon cancer cells and human colon tumors.
Colon cancer cell lines and immunohistochemistry were used.
E-cadherin expression was inversely related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic expression of COX-2 or Snail reduced E-cadherin and induced a scattered, flattened phenotype with few intercellular contacts in colon cancer cells. Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase expression, and increased the cells' motility. In addition, exposure to prostaglandin E(2) increased Snail expression and cell motility, and decreased E-cadherin expression. Membranous E-cadherin expression was lower in adenomas and cancers than in the adjacent, non-neoplastic epithelium. In contrast, the expressions of Snail and COX-2 were higher in cancers than in normal tissues and adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E-cadherin expression. Moreover, COX-2 expression was related to higher tumor stages and was significantly higher in nodal metastatic lesions than primary cancers.
This study suggests that COX-2 may have a role in tumor metastasis via EMT.
E-钙黏蛋白的下调是上皮-间质转化（EMT）的标志之一。癌细胞中 EMT 的进展与某些上皮标志物的丧失和间质表型的获得以及迁移活性有关。环氧合酶-2（COX-2）的表达与结肠癌的肿瘤侵袭和转移有关。本研究探讨了结肠癌细胞和人结肠癌组织中 E-钙黏蛋白与 COX-2 之间的关系。
使用结肠癌细胞系和免疫组织化学方法。
E-钙黏蛋白的表达与 COX-2 和 Snail 在结肠癌细胞中的表达呈负相关。COX-2 或 Snail 的异位表达降低了 E-钙黏蛋白的表达，并诱导结肠癌细胞呈现出分散、扁平的表型，细胞间接触较少。用佛波醇 12-肉豆蔻酸 13-乙酸酯处理癌细胞会增加 COX-2 和 Snail 的表达，降低 15-羟基前列腺素脱氢酶的表达，并增加细胞的迁移能力。此外，前列腺素 E（2）的暴露会增加 Snail 的表达和细胞迁移能力，并降低 E-钙黏蛋白的表达。腺瘤和癌症中的膜 E-钙黏蛋白表达低于相邻的非肿瘤上皮。相比之下，Snail 和 COX-2 的表达在癌症中高于正常组织和腺瘤。COX-2 的表达与异常 E-钙黏蛋白表达的区域增加有关。此外，COX-2 的表达与较高的肿瘤分期有关，在淋巴结转移病变中明显高于原发性癌症。
本研究表明 COX-2 可能通过 EMT 在肿瘤转移中发挥作用。
