Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas

Carcinoma cells become more motile and invasive via downmodulation of E-cadherin. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis. The aim of this study is to investigate the relationship between the expression of COX-2 and E-cadherin in a bladder cancer cell line and human bladder transitional cell carcinoma (TCCs). Phorbol 12-myristate 13-acetate (PMA) treatment for 5637 bladder cancer cells increased COX-2 expression, slightly induced Slug expression, and decreased E-cadherin expression. Ectopic expression of COX-2 or prostaglandin E2 (PGE2) treatment for 5637 cells reduced E-cadherin expression. This finding was confirmed by the result that knockdown of COX-2 expression or indomethacin administration increased the expression of E-cadherin. When compared with cells’ motility in serum-free medium, the treatment of PMA and PGE2 increased cell motility, and indomethacin treatment slightly decreased cell motility. In the tissues of bladder TCCs, COX-2 expression was inversely correlated with membranous E-cadherin expression and positively correlated with nuclear β-catenin expression. The expression of COX-2 and nuclear β-catenin expression was significantly higher in TCCs of high grade and invasive growth than in TCCs of low grade and noninvasive growth. In contrast, membranous E-cadherin expression was more decreased in tumors of high grade and invasive growth. In addition, nuclear β-catenin expression was significantly related to tumor recurrence. We suggest that COX-2 pathway reduces membranous E-cadherin expression in bladder TCCs and their expression pattern may provide important information in predicting the clinical behavior of bladder TCCs.