Kavoussi L R, Brown E J, Ritchey J K, Ratliff T L
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
J Clin Invest. 1990 Jan;85(1):62-7. doi: 10.1172/JCI114434.
Adjuvant intravesical Calmette-Guerin bacillus (BCG) is an effective treatment for superficial bladder cancer. The mechanisms by which BCG mediates antitumor activity are not known. We investigated the initial interaction of BCG with the bladder mucosa to determine whether binding was essential for the development of antitumor activity. Herein, we show that bladder urothelial disruption induced by acrolein, adriamycin, or electrocautery resulted in BCG binding in areas of urothelial damage. Binding induced by each method was inhibited by anti-fibronectin (FN) antibodies but not by antibodies to the basement membrane component laminin. Intravesical BCG binding also was inhibited by pretreating BCG with soluble FN. Inhibition of intravesical FN-mediated BCG attachment prevented immunization via the intravesical route. Moreover, the expression of both delayed hypersensitivity in the bladder of BCG-immunized mice and antitumor activity was inhibited by blocking FN-mediated intravesical BCG attachment. These data suggest that intralumenal attachment of BCG appears to be mediated by FN. Moreover, these data suggest that intravesical FN mediated attachment of BCG is a requisite step in BCG-mediated antitumor activity in the murine bladder tumor model.
辅助性膀胱内卡介苗（BCG）是浅表性膀胱癌的一种有效治疗方法。BCG介导抗肿瘤活性的机制尚不清楚。我们研究了BCG与膀胱黏膜的初始相互作用，以确定结合对于抗肿瘤活性的发展是否至关重要。在此，我们表明，丙烯醛、阿霉素或电灼诱导的膀胱尿路上皮破坏导致BCG在尿路上皮损伤区域结合。每种方法诱导的结合都被抗纤连蛋白（FN）抗体抑制，但不被基底膜成分层粘连蛋白的抗体抑制。膀胱内BCG结合也可通过用可溶性FN预处理BCG来抑制。抑制膀胱内FN介导的BCG附着可阻止通过膀胱内途径进行免疫。此外，通过阻断FN介导的膀胱内BCG附着，可抑制BCG免疫小鼠膀胱中的迟发型超敏反应和抗肿瘤活性。这些数据表明，BCG的腔内附着似乎是由FN介导的。此外，这些数据表明，膀胱内FN介导的BCG附着是小鼠膀胱肿瘤模型中BCG介导的抗肿瘤活性的一个必要步骤。
