title: Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced by growth factors through paracrine pathways.
abstract: Hyperplasia of transitional cell epithelium adjacent to human transitional cell carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a precancerous aberration. Alternatively, it has been suggested that the hyperplasia is due to paracrine action of tumour-derived growth factors. In this study we tested the latter hypothesis using 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 mice. Implantation of normal mouse bladder mucosa did not induce urothelial 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 transforming growth factor beta 1 (TGF beta 1). Similarly, TGF beta 1 inhibited the fibroblast growth factor-1 (FGF-1) and FGF-2 induced proliferation of g/G cells. Chemico-physical examination, bioassays with conditioned media, and RNA analysis of NUC-1 cells revealed that these cells secreted a growth factor with FGF-like properties. These results indicate that epithelial hyperplasia surrounding carcinomas is not necessarily a precancerous aberration, but may result from direct paracrine action of tumour-derived growth factors.
authors.affiliation: Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: W I
authors.initials: WI
authors.lastname: de Boer
authors.forename: J M
authors.initials: JM
authors.lastname: Rebel
authors.forename: C D
authors.initials: CD
authors.lastname: Thijssen
authors.forename: M
authors.initials: M
authors.lastname: Vermeij
authors.forename: A J
authors.initials: AJ
authors.lastname: van den Eijnden-Van Raaij
authors.forename: T H
authors.initials: TH
authors.lastname: van der Kwast
mesh_terms: D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned; D004261:DNA Replication / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia; D051379:Mice; D009092:Mucous Membrane; D009368:Neoplasm Transplantation; D013936:Thymidine / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004229:Dithiothreitol; D013936:Thymidine