Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer.
Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer.
复制标题
DOI：
10.17980/2016.1
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Mizoguchi E
中科院分区：
文献类型：
--
作者：
Subramaniam R;Mizoguchi A;Mizoguchi E
迄今为止，大量证据表明炎症性肠病（IBD）和结肠炎相关癌症（CAC）的发展之间存在显著关联。IBD的发病率/患病率在西方国家（包括美国、澳大利亚和英国）较高。虽然CAC的发展通常以遗传和表观遗传变化的逐步积累为特征，但慢性炎症如何导致CAC发展的确切机制在很大程度上是未知的。肠道炎症是CAC发生的主要影响因素之一。包括激活先天性和适应性免疫细胞中异常信号通路在内的粘液免疫应答在CAC中起关键作用。肿瘤进展和转移由严格控制的肿瘤微环境形成，该微环境由几种免疫细胞和基质细胞（包括巨噬细胞、嗜中性粒细胞、树突状细胞、髓源性抑制细胞、T细胞和肌成纤维细胞）协调。在这篇文章中，我们将讨论上皮细胞和免疫细胞信号传导在启动CAC肿瘤发生和粘膜免疫调节因子在结肠肿瘤微环境中的贡献因素。深入了解这些因素对于在不久的将来开发新的CAC抗炎和抗癌疗法是必要的。
To date, substantial evidence has shown a significant association between inflammatory bowel diseases (IBD) and development of colitis-associated cancer (CAC). The incidence/prevalence of IBD is higher in western countries including the US, Australia, and the UK. Although CAC development is generally characterized by stepwise accumulation of genetic as well as epigenetic changes, precise mechanisms of how chronic inflammation leads to the development of CAC are largely unknown. Preceding intestinal inflammation is one of the major influential factors for CAC tumorigenesis. Mucosal immune responses including activation of aberrant signaling pathways both in innate and adaptive immune cells play a pivotal role in CAC. Tumor progression and metastasis are shaped by a tightly controlled tumor microenvironment which is orchestrated by several immune cells and stromal cells including macrophages, neutrophils, dendritic cells, myeloid derived suppressor cells, T cells, and myofibroblasts. In this article, we will discuss the contributing factors of epithelial as well as immune cell signaling in initiation of CAC tumorigenesis and mucosal immune regulatory factors in the colonic tumor microenvironment. In depth understanding of these factors is necessary to develop novel anti-inflammatory and anti-cancer therapies for CAC in the near future.