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

We previously detected elevated transforming growth factor beta-1 (TGF-beta 1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-P expression in human bladder tumours. mRNA levels of TGF-beta 1, -beta 2 and -beta 3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta 1 protein levels were found to be higher in superficial tumours (T-a-T-1) (mean level of 0.153 ng mg(-1)) and in invasive T-2/T-3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T, tumours, however, contained only low amounts of TGF-beta 1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta 1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta 2 and TGF-beta 3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta 1 or TGF-beta 2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta 3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta 1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta 2 and -beta 3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer.