HYPERPLASIA OF EPITHELIUM ADJACENT TO TRANSITIONAL-CELL CARCINOMA CANBE INDUCED BY GROWTH-FACTORS THROUGH PARACRINE PATHWAYS

Hyperplasia of transitional cell epithelium adjacent to human transiti onal cell carcinomas (TCC) is a common finding in pathology. This hype rplasia may be a precancerous aberration. Alternatively, it has been s uggested that the hyperplasia is due to paracrine action of tumour-der ived growth factors. In this study we tested the latter hypothesis usi ng the mouse tumorigenic TCC cell line NUC-1. Transplantation of NUC-1 tumour cells into the urinary bladder submucosa of syngeneic mice in vivo induced hyperplasia of normal adjacent urothelium in all tested m ice. Implantation of normal mouse bladder mucosa did not induce urothe lial hyperplasia. In vitro, conditioned medium of NUC-1 cells induced the proliferation of the mouse urothelial cell line g/G, which closely resembles normal urothelial cells. This induction was inhibited by tr ansforming growth factor beta(1) (TGF beta(1)). Similarly, TGF beta(1) inhibited the fibroblast growth factor-1 (FGF-1) and FGF-2 induced pr oliferation of g/G cells. Chemico-physical examination, bioassays with conditioned media, and RNA analysis of NUC-1 cells revealed that thes e cells secreted a growth factor with FGF-like properties. These resul ts indicate that epithelial hyperplasia surrounding carcinomas is not necessarily a precancerous aberration, but may result from direct para crine action of tumour-derived growth factors.