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

Prostate Cancer and Prostatic Diseases volume 25, pages 463–471 (2022)Cite this article

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A Correction to this article was published on 22 June 2021

This article has been updated

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.

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Fig. 1: IBD is associated with a lymphocyte-rich tumor microenvironment in human prostate cancer.
Fig. 2: Dextran-sodium-sulfate (DSS) administration led to induction of chronic colitis in mice, mimicking human IBD.
Fig. 3: Chronic colitis is associated with prostatic immune cell infiltration.
Fig. 4: Chronic colitis is associated with intra-prostatic expression of pro-inflammatory cytokines.
Fig. 5: Chronic colitis is associated with prostatic pro-oncogenic AKT and NF-kB signaling, DNA damage, oxidative stress, and cell cycle arrest.

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Acknowledgements

This work was supported by the SPORE in Prostate Cancer (P50 CA180995) (JW, SAA, SDK). The project described was supported by the Robert H. Lurie Comprehensive Cancer Center, Northwestern University. We thank Northwestern University Histology and Phenotyping Core Laboratory for technical support which is supported by NCI P30-CA060553.

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Author notes

  1. Jennifer Ross

    Present address: ICON Central Laboratories, New York, NY, USA

  2. These authors contributed equally: Anuj S. Desai, Vinay Sagar

  3. These authors jointly supervised this work: Sarki A. Abdulkadir, Shilajit D. Kundu

Authors and Affiliations

  1. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    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, Jennifer Wu, Sarki A. Abdulkadir & Shilajit D. Kundu

  2. Department of Epidemiology and Biostatistics, University of California, San Francisco (UCSF), San Francisco, CA, USA

    Travis J. Meyers & John S. Witte

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Correspondence to Shilajit D. Kundu.

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Desai, A.S., Sagar, V., Lysy, B. et al. Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate. Prostate Cancer Prostatic Dis 25, 463–471 (2022). https://doi.org/10.1038/s41391-021-00392-7

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