Model of human transitional cell carcinoma: tumor xenografts in upper urinary tract of nude rat

Abstract

An in vivo model for the study of human transitional cell carcinoma (TCC) in the urinary tract is desirable. Orthotopic xenografts are useful in order to approximate better the behavior of human tumor cells in situ. Prior models have been described in the urinary bladder of the nude mouse and rat. We have developed the first model of implantation of human TCC in the upper urinary tract of an experimental animal. The kidneys of homozygous nude rats 4 weeks of age were inoculated with 1-5 x 10(6) cells of the RT4 well-differentiated papillary human TCC line through bilateral flank incisions, with transparenchymal injection of tumor cells into either the collecting system (renal pelvis) or the parenchyma. The overall implantation rate was 92% (54/59 kidneys). However, implantation into the collecting system occurred in only 45% (18/45) of the group. Ligation of the ureter prior to inoculation to produce urine stasis improved the mucosal implantation rate. Despite suspect urine cytology findings in the renal pelvis injection group, no distal seeding of the urinary tract was seen. Intraparenchymal tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumors. Vascular and lymphatic invasion were commonly seen; however, distant metastasis was not observed. This model will prove useful in determining the role of seeding in recurrent disease and in developing less invasive modalities for the treatment of upper tract TCC.