Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas

Abstract

We previously detected elevated transforming growth factor beta-1 (TGF-β1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-β expression in human bladder tumours. mRNA levels of TGF-β1, -β2 and -β3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-β1 protein levels were found to be higher in superficial tumours (T(a)-T1,) (mean level of 0.153 ng mg-1) and in invasive T2/T3, tumours (mean level of 0.104 ng mg-1) compared with normal urothelium (mean level of 0.065 ng mg-1). Invasive T4 tumours, however, contained only low amounts of TGF-β1 (mean level of 0.02 ng mg-1). Neither in mean nor in individual patients were serum and tissue TGF-β levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-β1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-β2 and TGF-β3 mRNA than normal epithelial cells Fibroblasts expressed about the same amount of TGF-β1 or TGF-β2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-β3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-β1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-β2 and -β3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-β serum levels and TGF-β expression in tumour tissue in bladder cancer.