Role of thymidine phosphorylase in an in vitro model of human bladder cancer invasion.

Journal article

PURPOSE: It has been previously demonstrated that the angiogenic factor thymidine phosphorylase is elevated significantly in invasive bladder cancer. We report that it is not merely an incidental finding. Thymidine phosphorylase has a functional role in bladder cancer invasion. MATERIALS AND METHODS: The superficial bladder cancer cell line RT112 was transfected by retroviral techniques to generate the RT112-TP clone that expressed significantly elevated levels of thymidine phosphorylase, comparable to those of invasive human bladder cancers. The empty vector control RT112-EV was generated for comparison. Growth of these transfectants was examined using a new in vitro model of bladder cancer invasion based on de-epithelialized rat bladder and by assessing growth as xenografts in nude mice. The effect of 5-deoxy-5-fluorouridine, a prodrug activated by TP to produce 5-fluorouracil, was also examined. RESULTS: RT112-TP high thymidine phosphorylase expressing cells invaded into the stroma of the in vitro model but wild-type RT112 and RT112-EV cells did not. This invasion was abolished by 5-deoxy-5-fluorouridine. Invasion correlated with thymidine phosphorylase expression on immunohistochemical testing. There was also a significantly greater xenograft growth rate for RT112-TP than for RT112-EV, confirming the malignant growth advantage conferred by thymidine phosphorylase. CONCLUSIONS: We demonstrated that thymidine phosphorylase may have a functional role in bladder cancer invasion and the apparent advantage of thymidine phosphorylase expression to tumor cells can be exploited by therapies that utilize prodrugs such as 5-deoxy-5-fluorouridine, which is activated by thymidine phosphorylase and inhibited invasion in our model.

Authors: Jones, A; Fujiyama, C; Turner, K; Cranston, D; Williams, K

• Publication status: Published
• Journal: Journal of urology
• Volume: 167
• Issue: 3
• Pages: 1482-1486
• Publication date: 2002-03-01
• DOI: 10.1097/00005392-200203000-00084
• EISSN: 1527-3792
• ISSN: 0022-5347
• Language: English
• Keywords: Humans; Tumor Cells, Cultured; Thymidine Phosphorylase; Rats; Carcinoma, Transitional Cell; Prodrugs; Neoplasm Invasiveness; Mice; Animals; Mice, Nude; Disease Models, Animal; Urinary Bladder Neoplasms; Transfection