TRANSURETHRAL BLADDER-TUMOR RESECTION ALTERS FIBRONECTIN EXPRESSION IN TRANSITIONAL CARCINOMA CELL-LINES

Purpose: To examine the effect of TGF beta 1 and post-transurethral re section of bladder tumor (TURBT) urine on fibronectin (FN) expression by transitional carcinoma (TCC) cell lines. Materials and Methods: Nor thern analysis and rtPCR for mRNA transcripts, in combination with ELI SA and immunohistochemistry for protein, were used to quantify the eff ect of TGF beta 1 and post-TURBT urine on cellular expression of FN in two TCC lines, 253J and 647V. The TGF beta 1-dependent nature of the response seen in post-TURBT urine was confirmed using exogenous TGF be ta 1 or blocking antibodies to TGF beta 1. Active and latent levels of TGFb1 were measured in post-TURBT urine and urine ''spiked'' cell cul ture media. Results: Baseline FN expression was low in the poorly diff erentiated, metastatic 253J line and high in the moderately differenti ated 647V line. TGF beta 1 and post-TURBT urine increased FN expressio n at both the mRNA and protein levels in the 253J line. Anti-TGF beta 1 antibodies inhibited the effect of post-TURBT urine on FN expression in 253J cells. High levels of TGF beta 1 decreased FN expression in 6 47V cells. Only latent TGF beta 1 was present in samples of urine and media. Conclusions: FN production in low expressing TCC lines can be a ugmented by exogenous TGF beta 1. TURBT increases latent urinary TGF b eta 1 which in turn affects TCC FN expression. Altered tumor expressio n of FN following TURBT may influence the effectiveness of intravesica l BCG.