Inhibition of bladder tumor cell implantation in cauterized urothelium, without inhibition of healing, by a fibronectin-related peptide (GRGDS).
BACKGROUND: Local recurrence after transurethral resection of bladder tumors (TURB) is common and might be diminished if free tumor cells within the bladder are prevented from reattaching. METHODS: In vitro inhibition of murine bladder tumor cells to an approximation of urothelial matrix with agents that might block attachment to components of the extracellular matrix, and in vivo inhibition of attachment in cautery-injured murine bladder. RESULTS: GRGDS, (0.1-2.5 mg/ml), a fibronectin-related peptide, mannose-6-phosphate, (0.1-20 mg/ml), a carbohydrate, and heparin (1-625 units/ml) all inhibited attachment in vitro in a dose-dependent fashion. YIGSR (0.1-2 mg/ml), a laminin-related peptide, did not. Mannose (10 mg/ml) did not significantly inhibit attachment of tumor cells to cauterized urothelium in vivo, whereas there was a 77% reduction of attachment in bladders irrigated with GRGDS (6.25 mg/ml) (p < 0.05), and the appearance of subsequent tumors in the bladder was inhibited. Finally, GRGDS (6.25 mg/ml) did not inhibit healing of the cautery ulcer. CONCLUSIONS: RGD-containing peptides may be useful as adjuvant therapy to decrease local recurrence after TURB and perhaps in other circumstances in which tumor cells spilled into a wound or body cavity threaten surgical success.