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Updated: Jun 14, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Evolution on experimental animal model for upper urothelium carcinogenesis.
Leonardo O Reis1, Wagner J Fávaro, Ubirajara Ferreira
1Department of Urology, Division of Urologic Oncology, School of Medicine, University of Campinas, R. Votorantim, 51, ap. 43, Campinas, SP, 13073-090, Brazil. reisleo@unicamp.br
A novel N-methyl-N-nitrosourea (MNU) and sodium citrate model effectively induces upper urinary tract tumors in rats. This model reveals matrix metalloproteinase (MMP)-dependent disruption of the dystroglycan (DG) complex in urothelial carcinogenesis.
Area of Science:
- Urothelial Carcinogenesis
- Experimental Pathology
- Animal Models
Background:
- Optimal animal models for upper urothelial carcinogenesis are lacking.
- This study addresses the need for a reproducible model to investigate upper urinary tract tumor development.
Purpose of the Study:
- To characterize histopathological features and molecular changes in a novel experimental model for upper urothelial carcinogenesis.
- To investigate the roles of alpha-dystroglycans (alpha-DG) and matrix metalloproteinase-9 (MMP-9) in tumor development.
Main Methods:
- Seventy-five female Fischer 344 rats were used, divided into control, N-methyl-N-nitrosourea (MNU), and MNU-citrate groups.
- Intravesical administration of MNU with or without sodium citrate was performed over 15 weeks.
- Bladder, ureters, and renal pelvis were analyzed for morphological and molecular changes.
Main Results:
- The MNU-citrate combination induced 100% upper urinary tract tumors, primarily high-grade noninvasive papillary urothelial carcinoma.
- The upper urothelium showed reduced alpha-DG and increased MMP-9 and Ki-67 in the MNU-citrate group.
- The MNU-only group developed 100% bladder tumors but no upper urothelial tumors.
Conclusions:
- The MNU-citrate model is a significant advancement for studying upper urinary tract carcinogenesis.
- MMP-dependent disruption of the DG complex is implicated in urothelial tumor development.
- This model can enhance understanding of human upper urothelial cancer and inform treatment strategies.
