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Updated: Mar 16, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model
Robert A Kazmierczak1,2, Bettina Gentry3, Tyler Mumm1,2
1Cancer Research Center, Columbia, Missouri, United States of America.
Abstract:
Attenuated Salmonella typhimurium injected in the circulatory system of mammals selectively targets tumors. Using weekly intraperitoneal injections of attenuated Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor development in the TRAMP prostate tumor mouse model, which utilizes SV40 early region expression for autochthonous formation of prostate tumors that progress into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent murine model. Thirteen weekly intraperitoneal administrations of 105-107 CFU CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice and histological analysis of TRAMP prostates at 22 weeks indicated that Salmonella monotherapy at administrated levels decrease visible tumor size (>29%) but did not significantly inhibit previously described SV40 expression-driven TRAMP tumor progression to undifferentiated carcinomas when histologically examined. In conclusion, this work demonstrates baseline results for CRC2631 Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in preparation for study of combination therapies that resolve autochthonously generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate tumor progression.
Insights
Attenuated Salmonella typhimurium (CRC2631) reduced visible tumor size in a mouse prostate cancer model. However, it did not significantly inhibit tumor progression, suggesting potential for combination therapies.
Area of Science:
- Oncology
- Microbiology
- Immunology
Background:
- Attenuated Salmonella typhimurium demonstrates selective tumor targeting in mammals.
- The TRAMP mouse model spontaneously develops prostate tumors, progressing to metastatic carcinomas.
Purpose of the Study:
- To evaluate the efficacy of Salmonella strain CRC2631 as monotherapy for prostate tumor regression and inhibition in the TRAMP model.
- To establish baseline data for CRC2631 monotherapy in preparation for combination therapy studies.
Main Methods:
- Weekly intraperitoneal injections of attenuated Salmonella strain CRC2631 (10^5-10^7 CFU) were administered to 10-week-old TRAMP mice.
- Tumor development and progression were assessed via histological analysis at 22 weeks.
Main Results:
- Salmonella monotherapy was well tolerated in the TRAMP mouse model.
- A statistically significant decrease in visible tumor size (>29%) was observed.
- No significant inhibition of SV40-driven tumor progression to undifferentiated carcinomas was detected.
Conclusions:
- CRC2631 Salmonella monotherapy shows potential for reducing prostate tumor size in the TRAMP model.
- Further research is needed to explore combination therapies to enhance tumor regression and inhibit progression.
