Epidermal growth factor--interactions with normal and malignant urothelium: in vivo and in situ studies

Epidermal growth factor (EGF) is excreted in urine in high concentrations and thus incubates with bladder epithelial cells continuously. However, it is not known whether any urothelial cells can bind urinary EGF or respond to it. Using a monoclonal antibody (528) to the binding portion of the human EGF receptor, immunoperoxidase staining demonstrated that the basal cell layer of normal urothelium is richly endowed with cell surface EGF receptors while the superficial cell layer is not. Alternatively, superficial cells of premalignant and malignant urothelium have many surface EGF receptors. Intravesical EGF induces in vivo activity of ornithine decarboxylase and DNA synthesis in rat bladders, with nuclear thymidine incorporation being limited to the basal epithelial cell layer. These studies indicate that urothelium can respond to urinary EGF and that this response parallels the distribution of EGF receptors. These findings combined with the difference in EGF-receptor expression between malignant and normal cells indicate that urinary EGF may play a role in bladder tumor development and/or growth.