Development of Traceable Mouse Models of Advanced and Metastatic Bladder Cancer

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Bladder cancer (BC) presents a poor prognosis, especially in advanced and metastatic stages.
• A critical need exists for advanced, particularly metastatic, BC mouse models to test novel therapies.
• Existing models often fail to accurately recapitulate human BC pathology and treatment responses.

Purpose of the Study:

• To develop and validate novel, traceable mouse models of advanced muscle-invasive bladder cancer (MIBC).
• To create models that accurately reflect human BC complexity, including metastasis and immune microenvironment.
• To establish a platform for testing therapeutic strategies and understanding treatment resistance in BC.

Main Methods:

• Developed a genetically engineered mouse model by deleting tp53 and pten genes, incorporating Firefly luciferase (Luc) and SIY T-cell antigen.
• Validated tumor development, bioluminescence tracking, and immune microenvironment composition.
• Created a second model via orthotopic injection of BC cell lines, assessing muscle invasion and metastasis rates.

Main Results:

• The engineered model allowed bioluminescent tracking of tumor progression without altering tumor development or immune microenvironment.
• The model demonstrated unresponsiveness to anti-PD-1 treatment, mirroring human BC patient responses.
• The orthotopic injection model showed 83% metastasis development and muscle layer invasion, enabling in vivo visualization.

Conclusions:

• The developed traceable mouse models closely mimic human advanced bladder cancer, including metastasis and treatment resistance.
• These models serve as valuable tools for in vivo tracking of tumor progression, metastasis, and therapeutic response evaluation.
• This work enhances the available resources for fundamental and translational research in bladder cancer.