FIBRONECTIN-MEDIATED CALMETTE-GUERIN BACILLUS ATTACHMENT TO MURINE BLADDER MUCOSA - REQUIREMENT FOR THE EXPRESSION OF AN ANTITUMOR RESPONSE
FIBRONECTIN-MEDIATED CALMETTE-GUERIN BACILLUS ATTACHMENT TO MURINE BLADDER MUCOSA - REQUIREMENT FOR THE EXPRESSION OF AN ANTITUMOR RESPONSE
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DOI：
10.1172/jci114434
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发表时间：
1990-01-01
影响因子：
15.9
通讯作者：
RATLIFF, TL
中科院分区：
文献类型：
--
作者：
KAVOUSSI, LR;BROWN, EJ;RATLIFF, TL
卡介苗（BCG）膀胱灌注是治疗浅表性膀胱癌的有效方法。BCG介导抗肿瘤活性的机制尚不清楚。我们研究了BCG与膀胱粘膜的初始相互作用，以确定结合是否是发展抗肿瘤活性所必需的。在此，我们表明，膀胱尿路上皮破坏引起的丙烯醛，阿霉素，或电灼导致卡介苗结合在尿路上皮损伤的地区。 每种方法诱导的结合被抗纤连蛋白（FN）抗体抑制，但不被基底膜组分层粘连蛋白的抗体抑制。用可溶性FN预处理BCG也可抑制膀胱内BCG结合。膀胱内FN介导的BCG附着的抑制阻止了通过膀胱内途径的免疫。此外，通过阻断FN介导的BCG膀胱内粘附，BCG免疫小鼠膀胱迟发性超敏反应和抗肿瘤活性的表达均被抑制。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BCG介导的抗肿瘤活性在小鼠膀胱肿瘤模型中的必要步骤。
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.