Department of Molecular Medicine, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
Cells. 2023 Jan 31;12(3):459. doi: 10.3390/cells12030459.
Mast cells are tissue-resident sentinels involved in large number of physiological and pathological processes, such as infection and allergic response, thanks to the expression of a wide array of receptors. Mast cells are also frequently observed in a tumor microenvironment, suggesting their contribution in the transition from chronic inflammation to cancer. In particular, the link between inflammation and colorectal cancer development is becoming increasingly clear. It has long been recognized that patients with inflammatory bowel disease have an increased risk of developing colon cancer. Evidence from experimental animals also implicates the innate immune system in the development of sporadically occurring intestinal adenomas, the precursors to colorectal cancer. However, the exact role of mast cells in tumor initiation and growth remains controversial: mast cell-derived mediators can either exert pro-tumorigenic functions, causing the progression and spread of the tumor, or anti-tumorigenic functions, limiting the tumor's growth. Here, we review the multifaceted and often contrasting findings regarding the role of the intestinal mast cells in colon cancer progression focusing on the molecular pathways mainly involved in the regulation of mast cell plasticity/functions during tumor progression.
肥大细胞是组织驻留的哨兵,由于表达广泛的受体,参与许多生理和病理过程,如感染和过敏反应。肥大细胞也经常在肿瘤微环境中观察到,这表明它们在从慢性炎症向癌症的转变中发挥了作用。特别是,炎症与结直肠癌发展之间的联系越来越清楚。长期以来,人们一直认为炎症性肠病患者患结肠癌的风险增加。来自实验动物的证据也表明,固有免疫系统参与了散发性发生的肠腺瘤(结直肠癌的前体)的发展。然而,肥大细胞在肿瘤起始和生长中的确切作用仍存在争议:肥大细胞衍生的介质可以发挥促肿瘤作用,导致肿瘤的进展和扩散,也可以发挥抗肿瘤作用,限制肿瘤的生长。在这里,我们综述了关于肠道肥大细胞在结肠癌进展中的作用的多方面且常常相互矛盾的发现,重点关注在肿瘤进展过程中主要参与调节肥大细胞可塑性/功能的分子途径。