EGF, TGF alpha, AR and HB-EGF are autocrine growth factors for human bladder carcinoma cell lines.

We have previously shown that the epidermal growth factor receptor (EGFR) is involved in the growth regulation of human bladder carcinoma cells. Here we have analysed a series of bladder carcinoma cell lines adapted to serum-free growth for the expression of EGFR ligands. Most of the cells were shown to produce EGF, TGF alpha, AR and HB-EGF. By using neutralizing antibodies we could show that all of these factors were also involved in the stimulation of the cells. Moreover, recombinant factors were able to stimulate growth as well as receptor-linked extracellular acidification. This indicates the direct growth regulatory role of these ligands, and that the EGFR and its ligands provide an autocrine pathway that is likely to be important for the malignancy of these tumors.