The expression of cyclooxygenase in transitional cell carcinoma cell lines: its correlation with tumor differentiation, invasiveness and prostanoids production.

Abstract

To evaluate the isozyme activities of COX-1 and COX-2 in TCC cells and correlate with cellular differentiation and tumor behavior. Various TCC cell lines were characterized through several aspects: (1). to measure the content and the mRNA amount of COX-1 and COX-2, (2). to characterize the proteins of COX-1 and COX-2 by Western immunoblotting, (3). to measure the production of prostaglandin E2 and thromboxane B2 in culture media, and (4). to correlate these parameters with tumor differentiation and invasiveness. Seven out of 10 cell lines (70%) had significantly higher COX expression than normal urothelium. Tumors with lower-grade differentiation and less invasiveness had significantly higher content of COX-1 and COX-2 than those tumors with higher-grade differentiation and more invasive behavior (p<0.01). The expression of COX mRNA in TSGH8301, TCC8702 and RT4 were much higher than J82 which has minimal expression of COXs. Similarly, the COX-2 protein was much higher in TSGH8301, TCC8702 and RT4 when compared with J82. TSGH8301, TCC8702, and RT4 had high production of PGE2 and thromboxane B2 in their culture media. Increased secretions of PGE2 and thromboxane B2 were also observed in TCC8701, TCC9101, HT1376, and T24. The production of prostanoids is closely related to cytoplasmic COX expression of tumor cells. The expression of COX-1 and COX-2 is a common phenomenon in TCC cells and closely related to cellular differentiation and tumor invasiveness. The COX-2 inhibitors may play an important role in the control of TCC growth.