Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate

Anuj S. Desai, Vinay Sagar, Barbara Lysy, Adam B. Weiner, Oliver S. Ko, Conor Driscoll, Yara Rodriguez, Rajita Vatapalli, Kenji Unno, Huiying Han, Jason E. Cohen, Amanda X. Vo, Minh Pham, Michael Shin, Ketan Jain-Poster, Jennifer Ross, Elizabeth G. Morency, Travis J. Meyers, John S. Witte, Jennifer WuSarki A. Abdulkadir, Shilajit D. Kundu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Inflammatory bowel disease (IBD) has been implicated as a risk factor for prostate cancer, however, the mechanism of how IBD leads to prostate tumorigenesis is not known. Here, we investigated whether chronic intestinal inflammation leads to pro-inflammatory changes associated with tumorigenesis in the prostate. Methods: Using clinical samples of men with IBD who underwent prostatectomy, we analyzed whether prostate tumors had differences in lymphocyte infiltrate compared to non-IBD controls. In a mouse model of chemically-induced intestinal inflammation, we investigated whether chronic intestinal inflammation could be transferred to the wild-type mouse prostate. In addition, mouse prostates were evaluated for activation of pro-oncogenic signaling and genomic instability. Results: A higher proportion of men with IBD had T and B lymphocyte infiltration within prostate tumors. Mice with chronic colitis showed significant increases in prostatic CD45 + leukocyte infiltration and elevation of three pro-inflammatory cytokines—TIMP-1, CCL5, and CXCL1 and activation of AKT and NF-kB signaling pathways. Lastly, mice with chronic colitis had greater prostatic oxidative stress/DNA damage, and prostate epithelial cells had undergone cell cycle arrest. Conclusions: These data suggest chronic intestinal inflammation is associated with an inflammatory-rich, pro-tumorigenic prostatic phenotype which may explain how gut inflammation fosters prostate cancer development in men with IBD.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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