Abstract 5344: Myeloid populations upregulated in prostate cancer are associated with colitis induced colorectal cancer

Abstract

Abstract Chronic systemic inflammation caused by diseases like ulcerative colitis (UC) and Crohn’s disease (CD) increases the risk of developing colorectal cancer (CRC). Research indicates that patients with UC are more susceptible to prostate cancer (PCa) and individuals with PCa may also be at a higher risk for developing CRC. However, these relationships are not well defined. Here, we explored these relationships using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and in young and aged healthy wild-type mice and conditional transgenic mice harboring Pten-deficient (KO) or Pten/Trp53-deficient (DKO) PCa. After a 25-week follow-up, DSS-induced UC caused more severe colitis in prostate tumor-bearing DKO compared to healthy WT mice. None of the DSS WT mice developed tumors, whereas 75% (3/4 mice) of DSS DKO mice did, including two out of four mice that developed multiple tumors. Overall, DKO mice with prostate tumors had increased levels of CD11b+/Gr1+ in peripheral blood, prostate, and colon compared with WT mice. Quantitative immunohistochemical analyses revealed that DKO mice with prostate tumors had a significantly higher 2.8-fold increase in the levels of Gr1+ cells in the colon compared to heathy WT mice. Overall, DSS-induced colitis further increased Gr1+ cells in the colon of WT and DKO mice by 2.5- and 2-fold, respectively. Gr1+ cells comprised 3.0%, 4.7%, and 10.1% of cells in normal colon from control WT mice and inactive and active regions of the colon in DSS-exposed WT mice, respectively. In DKO mice, Gr1+ cells comprised 7.0%, 19.2%, and 23.6% of cells in normal colon from control mice and inactive and active regions of the colon in DSS-exposed mice, respectively. CD68+, which corresponds to M1 polarized macrophages comprised 0.9%, 1.8%, and 20.6% of cells in normal colon from control WT mice and inactive and active regions of the colon in DSS-exposed WT mice, respectively, However, in DKO mice CD68+ cells comprised 3.0%, 2.8% and 1.6% of cells in normal colon from control mice and inactive and active regions of the colon in DSS-exposed mice, respectively. Our study suggests that Gr1 cells that were abundant in PCa-bearing mice were also present in colons and could have contributed to CRC. Moreover, CD68+ macrophages in the colons of healthy mice may have decreased tumor promoting effects of DSS. This study provides preclinical evidence showing that systemic inflammation in the presence of an existing malignancy increases the risk of a second malignancy, in this case linking PCa to colitis-induced-CRC. Citation Format: Yurie Kura, Marco A. De Velasco, Kazuko Sakai, Mamoru Hashimoto, Syogo Adomi, Takafumi Minami, Kazuhiro Yoshimura, Kazutoshi Fujita, Kazuto Nishio, Hirotsugu Uemura. Myeloid populations upregulated in prostate cancer are associated with colitis induced colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5344.