Animal Models in Bladder Cancer

Abstract

Background: Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with an increasing incidence and mortality. Mouse models of bladder cancer should possess a high value of reproducibility, predictability, and translatability to allow mechanistic, chemo-preventive, and therapeutic studies that can be furthered into human clinical trials.

Objectives: To provide an overview and resources on the origin, molecular and pathological characteristics of commonly used animal models in bladder cancer.

Methods: A PubMed and Web of Science search was performed for relevant articles published between 1980 and 2021 using words such as: "bladder" and/or "urothelial carcinoma" and animal models. Animal models of bladder cancer can be categorized as autochthonous (spontaneous) and non-autochthonous (transplantable). The first are either chemically induced models or genetically engineered models. The transplantable models can be further subclassified as syngeneic (murine bladder cancer cells implanted into immunocompetent or transgenic mice) and xenografts (human bladder cancer cells implanted into immune-deficient mice). These models can be further divided-based on the site of the tumor-as orthotopic (tumor growth occurs within the bladder) and heterotopic (tumor growth occurs outside of the bladder).

Keywords: animal models; bladder cancer; urothelial cancer; xenografts.

Figure 1

Schematic illustration of the pathological stages of urothelial cancer of the bladder, therapeutic intervention, environmental, genetic, and molecular influences of urothelial carcinogenesis, progression, and metastasis. Opportunities for diagnostic/prognostic biomarker discovery are shown compared to disease stage. (Adapted from© Bincy Anu John1 and Neveen Said, Insights from animal models of bladder cancer: recent advances, challenges, and opportunities, Oncotarget, 2017, Vol. 8, (No. 34) [12]). CIS—carcinoma in situ; TURBT—transurethral resection of bladder tumor; BCG—Bacillus Calmette–Guérin; GSMT—glycine sarcosine methyltransferase; NAT—N-acetyltransferase; ROS/RNS—Reactive oxygen and nitrogen species; DNA—desoxyribonucleic acid; EMT—epithelial to mesenchymal transition.

Figure 2

Summary of the available mouse models of urinary bladder cancer (© Bincy Anu John1 and Neveen Said, Insights from animal models of bladder cancer: recent advances, challenges, and opportunities, Oncotarget, 2017, Vol. 8, (No. 34) [12]).