Momose H, Uchida K, Kakinuma H, Yura Y, Oyasu R
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Cancer Lett. 1990 Sep;53(2-3):91-6. doi: 10.1016/0304-3835(90)90199-8.
The role of urine in epithelial-stromal interactions in urinary bladder carcinogenesis was investigated using the 'Stroma' bladder model established in our laboratory. Rats treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) in drinking water for 4 weeks or age-matched untreated rats served as donors of bladders with denuded epithelium ('stroma' bladders), which were resurfaced 4 days later with urothelial cells from rats treated with 0.05% BHBN for 4 weeks. Subsequently, the transplants received weekly injections of normal rat urine or saline. In the urine-free environment, cell implants developed hyperplastic changes but few tumor formations with no significant difference between the two types of 'stroma' bladder. In contrast, urine instillation stimulated neoplastic growth, and tumor-enhancing effect was significantly accelerated in the BHBN-treated 'stroma' bladder group as compared to the control group. These results suggest that epithelial-stromal interactions are altered in such a way that bladder carcinogenesis is enhanced by prior exposure of the bladder stroma to carcinogen and subsequent urine contact.
利用我们实验室建立的“基质”膀胱模型，研究了尿液在膀胱致癌过程中上皮-基质相互作用中的作用。给大鼠饮用含0.05% N-丁基-N-(4-羟基丁基)亚硝胺（BHBN）的水4周，或使用年龄匹配的未处理大鼠作为膀胱供体，制备去上皮的“基质”膀胱，4天后用经0.05% BHBN处理4周的大鼠的尿路上皮细胞重新覆盖。随后，给移植体每周注射正常大鼠尿液或生理盐水。在无尿环境中，细胞植入物出现增生性改变，但肿瘤形成较少，两种类型的“基质”膀胱之间无显著差异。相比之下，尿液灌注刺激肿瘤生长，与对照组相比，经BHBN处理的“基质”膀胱组的肿瘤促进作用明显加速。这些结果表明，上皮-基质相互作用发生了改变，使得膀胱基质预先暴露于致癌物并随后接触尿液会增强膀胱癌的发生。
