Role of Fibronectin in Intravesical BCG Therapy for Superficial Bladder Cancer

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Abstract
Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both of prophylaxis and treatment of superficial bladder cancer. In order to identify the progression for events that result in BCG-mediated antitumor actiivty, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix protiens to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.