PURPOSE: An in vivo tumor model for the study of human urothelial carcinoma is desirable. Orthotopic xenografts are useful in order to better approximate human tumor cell behavior in situ. A prior model has been described in the nude mouse. However, its small bladder size limits both histologic characterization and the application of intravesical therapeutics. In the absence of preirradiation, orthotopic xenografts of human transitional cell carcinoma in the nude rat has not been previously reported. MATERIALS AND METHODS: Nude rats 2 to 4 weeks of age were inoculated with 1-5 x 10(6) cells of RT4 (well differentiated papillary human bladder tumor cell line). Inoculation was performed via open cystotomy. Techniques of mucosal injury including acid treatment and cautery were explored in an effort to optimize tumor implantation and growth. Animals were sacrificed at varying intervals and histologic assessment was performed. RESULTS: The overall rate of tumor implantation and growth was 93.4% (57 of 61). Tumors reliably grew within the muscularis and mucosal growth was seen as well. Intramuscular tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumor. Tumor growth was consistently seen as early as 2 weeks after inoculation which facilitates experimental trials. Distant metastasis was not observed. Mucosal injury did not increase the rate of tumor implantation. CONCLUSION: This model is highly reproducible and will prove useful in the further study of bladder cancer progression as well as in the development of therapeutic modalities for both superficial and muscle invasive bladder carcinoma.
PURPOSE: An in vivo tumor model for the study of humanurothelial carcinoma is desirable. Orthotopic xenografts are useful in order to better approximate humantumor cell behavior in situ. A prior model has been described in the nude mouse. However, its small bladder size limits both histologic characterization and the application of intravesical therapeutics. In the absence of preirradiation, orthotopic xenografts of human transitional cell carcinoma in the nude rat has not been previously reported. MATERIALS AND METHODS: Nude rats 2 to 4 weeks of age were inoculated with 1-5 x 10(6) cells of RT4 (well differentiated papillary humanbladder tumor cell line). Inoculation was performed via open cystotomy. Techniques of mucosal injury including acid treatment and cautery were explored in an effort to optimize tumor implantation and growth. Animals were sacrificed at varying intervals and histologic assessment was performed. RESULTS: The overall rate of tumor implantation and growth was 93.4% (57 of 61). Tumors reliably grew within the muscularis and mucosal growth was seen as well. Intramuscular tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumor. Tumor growth was consistently seen as early as 2 weeks after inoculation which facilitates experimental trials. Distant metastasis was not observed. Mucosal injury did not increase the rate of tumor implantation. CONCLUSION: This model is highly reproducible and will prove useful in the further study of bladder cancer progression as well as in the development of therapeutic modalities for both superficial and muscle invasive bladder carcinoma.
Authors: Alexander Gelbard; Michael E Kupferman; Samar A Jasser; Wantao Chen; Adel K El-Naggar; Jeffrey N Myers; Ehab Y Hanna Journal: Clin Cancer Res Date: 2008-11-15 Impact factor: 12.531