Development of a novel immunocompetent murine tumor model for urothelial carcinoma using in vivo electroporation.

Autor: Soleder S; Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany. stefan.soleder@gmail.com.; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolph-Krehl-Str. 13-17, 68167, Mannheim, Germany. stefan.soleder@gmail.com., Gengenbacher N; Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolph-Krehl-Str. 13-17, 68167, Mannheim, Germany., Mogler C; Department of Pathology, Technical University of Munich, Munich, Germany., Eckstein M; Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen- Nürnberg, Erlangen, Germany., Runge A; Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany., Kriegmair MC; Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.; Department of Urology, University Hospital Mannheim, Mannheim, Germany., Augustin HG; Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany. augustin@angioscience.de.; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolph-Krehl-Str. 13-17, 68167, Mannheim, Germany. augustin@angioscience.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 27; Vol. 14 (1), pp. 25619. Date of Electronic Publication: 2024 Oct 27.
DOI: 10.1038/s41598-024-77178-z
Abstrakt: A lack of advanced preclinical mouse tumor models impedes the progress in urothelial carcinoma research. We present here a novel fast, robust, reliable, and highly reproducible model for the genetic induction of bladder cancer in immunocompetent mice. Different sets of oncogenic transposons (Cmyc, Kras) and Cre drivers were transfected into the murine bladder wall of two different genetic backgrounds (Trp53 fl/fl and Braf V600E , Pten fl/fl , Ctnnb1 exon3-fl/fl ). Transfection was carried out using in vivo electroporation of the bladder after surgical exploration and transmural or transurethral intravesical plasmid injection. Up to 100% of animals developed urothelial carcinomas of the bladder. Time to tumor onset ranged from 16 to 97 days with a median of approximately 23 days in the fastest groups. Histological examination identified orthotopic urothelial carcinomas in most cases, in some experimental groups up to 100%. The resulting tumors were highly invasive and often metastatic. Metastases were found in up to 100% of tumor bearing mice per group. Taken together, this study establishes the proof-of-principle that in vivo electroporation can be versatilely employed as a reliable, fast, and robust method for the highly reproducible induction of urothelial carcinomas in the murine bladder wall. This novel murine tumor model could pave the way towards more easily modelling subtype specific urothelial carcinomas in mice.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje