Development of Traceable Mouse Models of Advanced and Metastatic Bladder Cancer.

Details

Serval ID
serval:BIB_3103A9E7A8CA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development of Traceable Mouse Models of Advanced and Metastatic Bladder Cancer.
Journal
Cancers
Author(s)
Desponds E., Kioseoglou K., Zdimerova H., Ongaro M., Verdeil G., Leblond M.M.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
17/06/2024
Peer-reviewed
Oui
Volume
16
Number
12
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Bladder cancer (BC) is the fourth most common cancer in men, with a poor patient prognosis for advanced disease. The poor survival of patients with muscle-invasive bladder cancer (MIBC) and metastatic status emphasizes the urgent need to develop new therapies. Lacking in the field of BC is the availability of relevant advanced BC mouse models, especially metastatic ones, that accurately recapitulate the complexities of human pathology to test and study new therapeutic strategies. Addressing this need, we developed a traceable mouse model of BC that expresses tumor-associated antigens within the context of advanced muscle-invasive BC. This novel system was achieved through the deletion of the tp53 and pten genes, alongside the incorporation of the fusion construct of Firefly luciferase (Luc) and the SIYRYYGL (SIY) T-cell antigen. We validate that the presence of the transgene did not impact on the development of the tumors while allowing us to measure tumor progression by bioluminescence. We show that the transgene did not influence the composition of the immune tumor microenvironment. More importantly, we report that this model was unresponsive to anti-PD-1 treatment, as in the majority of patients with BC. We also develop a new model based on the orthotopic injection of BC clonal cell lines derived from our first model. We demonstrate that this new model invades the muscle layer and has a metastasis development rate of 83%. The advantage of this model is that we can visualize tumor growth and metastasis development in vivo. These mouse models' characteristics, displaying many similarities with the human pathology, provide a valuable tool for tracking tumor progression, metastasis spread in vivo, and treatment resistance, as well as exploring fundamental and translational aspects of BC biology. This work contributes to the improvement in the landscape of mouse models of advanced BC for testing new therapeutic strategies.
Keywords
bladder cancer, metastasis, mouse model
Pubmed
Web of science
Open Access
Yes
Create date
05/07/2024 10:08
Last modification date
06/07/2024 6:06
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