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 wi thin the bladder are prevented from reattaching. Methods: In vitro inh ibition of murine bladder tumor cells to an approximation of urothelia l 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 d ose-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 7 7% reduction of attachment in bladders irrigated with GRGDS (6.25 mg/m l) (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 a s adjuvant therapy to decrease local recurrence after TURB and perhaps in other circumstances in which tumor cells spilled into a wound or b ody cavity threaten surgical success.