Abstract 312: A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: A causative role for infectious agents and chronic inflammation in prostate cancer etiology has been difficult to establish in humans. To study this potential link in an in vivo system, we have developed a mouse model of long-term bacteria-induced chronic inflammation of the prostate using a prostatectomy-derived strain of Propionibacterium acnes that may be of particular relevance to prostate cancer. Methods: Prostates of C57BL/6J mice were inoculated, via urethral catheterization, with PBS (control) or a strain of P. acnes (PA2) isolated from human prostatectomy tissues. Animals were assessed at 2 days, 1 week, 2 weeks, or 8 weeks post-inoculation via histology and immunohistochemistry (IHC). Results: PA2 inoculation resulted in severe acute and chronic inflammation confined to the dorsal lobe of the prostate. Chronic inflammatory infiltrates persisted for at least 8 weeks post-inoculation. Inflammatory lesions were associated with an increase in the Ki-67 proliferative index, and diminished Nkx3.1 and androgen receptor (AR) production. Interestingly, the observed response required live bacteria. Additionally, both IHC and in situ hybridization assays for P. acnes indicated a potential intracellular persistence of P. acnes in prostate epithelial cells. Conclusions: To our knowledge, this is the first mouse model of long-term prostatic inflammation induced by P. acnes, and more generally, any prostatectomy tissue-derived bacterial isolate. This model may serve as a valuable preclinical model of chronic prostatic inflammation that can be used to mechanistically study the link between inflammation and prostate cancer and other prostate disease. Citation Format: Debika Biswal Shinohara, Ajay Vaghasia, Shu-Han Yu, William G. Nelson, Angelo M. De Marzo, Srinivasan Yegnasubramanian, Karen S. Sfanos. A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 312. doi:10.1158/1538-7445.AM2013-312