Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model

PLoS One. 2016 Aug 9;11(8):e0160926. doi: 10.1371/journal.pone.0160926. eCollection 2016.

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.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / microbiology*
  • Adenocarcinoma / pathology*
  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Immunization
  • Injections
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasm Grading
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / microbiology*
  • Prostatic Neoplasms / pathology*
  • Salmonella typhimurium / physiology*
  • Tumor Burden*

Grants and funding

This work was funded internally by the Cancer Research Center, Columbia, MO, USA. http://cancerresearchcenter.org/.