Heparin Prevention of Tumor Cell Adherence and Implantation on Injured Urothelial Surfaces

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Abstract
Increasing laboratory and clinical evidence supports the concept of tumor cell implantation as a cause of intravesical recurrence in transitional cell carcinoma of the bladder. The integrity of the surface mucopolysaccharide layer of the bladder has been shown to be crucial in preventing bacterial or crystalline adherence. The purpose of this study was to evaluate the effects of bladder surface mucin integrity on tumor cell adherence and implantation. The adherence of tumor cells to in situ bladders which were either normal, injured, or injured and subsequently heparin-coated was studied using a radiolabeled tumor cell adherence assay. The mechanism of action of heparin in reducing tumor cell adherence and cytotoxic effects of heparin on tumor cells were evaluated. Finally, the ability of topical heparin to reduce tumor implantation rates on injured urothelial surfaces was studied. Urothelial injury by either dilute acid or fulguration resulted in markedly increased tumor cell adherence compared to normal. Topical heparin was capable of reducing cell adherence in injured bladders to control levels. Bladder coating with heparin rather than tumor cell coating was found to be the critical determinant in preventing tumor cell adherence. Heparin had no cytotoxic effects in any of the assays used. The implantation rate in heparin coated bladder was 19% compared to 50% in non-coated bladders. This study suggests that the bladder surface mucopolysaccharide layer plays a critical role in preventing tumor cell adherence and subsequent implantation. Restoration of this layer via exogenous topical heparin is capable of restoring the anti-adherence integrity to the bladder surface.