由溃疡性结肠炎 (UC) 和克罗恩病 (CD) 等疾病引起的慢性全身炎症会增加患结直肠癌 (CRC) 的风险。最近的证据表明，UC 患者更容易患前列腺癌 (PCa)，PCa 患者患 CRC 的风险也可能更高。然而，这些关系并没有得到很好的定义。更好地了解这种现象可以改善对高风险人群的识别。在本研究中，我们通过使用葡聚糖硫酸钠 (DSS) 诱导的结肠炎 (DSS-UC) 和 DSS/氧化偶氮甲烷 (AOM) 诱导的 CRC (DSS/AOM-CRC) 野生型临床前小鼠模型的实验来表征这些关系和 PCa 的条件转基因小鼠。我们发现，在患有 PCa 的小鼠中，DSS 诱导的 UC 更为严重，并且在没有 AOM 的情况下导致 CRC 的发展。我们进一步表明，发展为 DSS 诱导的 UC 的无 PCa 小鼠也在正常前列腺中表现出类似于增殖性炎症萎缩的组织学变化。最后，我们使用免疫组织化学免疫分析表明，患有 PCa 诱导的慢性全身炎症的小鼠在正常结肠中积累了 Gr1 髓样细胞，并且暴露于 DSS 进一步在活动性结肠炎区域和结肠肿瘤中富集了这些细胞。我们的研究提供了证据支持全身性慢性炎症与癌症之间的联系。© 2024。作者获得日本人类细胞协会的独家许可。

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer.© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.