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Estrogen inhibits the growth of colon cancer in mice through reversing extracellular vesicle-mediated immunosuppressive tumor microenvironment
Cancer Letters ( IF 9.7 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.canlet.2021.08.011
Lingling Jiang 1 , Haiyi Fei 1 , Anran Yang 1 , Jiajuan Zhu 2 , Jindan Sun 2 , Xiu Liu 1 , Wenzhi Xu 1 , Jianhua Yang 1 , Songying Zhang 1
Affiliation  

Postmenopausal women taking estrogen supplements are at a lower risk of advanced colorectal cancer, but the underlying mechanism remains unclear. Thus, this study examined the role of estrogen in colorectal cancer. Estrogen receptor expression levels in in situ colorectal cancer tissue from female patients increased significantly, indicating their estrogen sensitivity. Compared with the sham-operated group, the growth of MC38 tumors was enhanced in ovariectomized mice, which was reversed in ovariectomized mice with E2 supplementation. The PD-L1+ M2-like macrophage, regulatory T (Treg) cell, and myeloid-derived suppressor cell (MDSC) populations significantly increased, and the population of cytotoxic CD8+ T cells declined in MC38 tumors in ovariectomized mice, which were all reversed in ovariectomized mice with E2 supplementation. MC38 cell-derived extracellular vesicles (MC38-EVs), but not EVs derived from MC38 cells treated with E2 (E2-MC38-EVs), were involved in the establishment of immunosuppressive tumor microenvironment. E2-MC38-EVs contained lower TGF-β1 levels and were less capable of inducing Treg cells than MC38-EVs in vitro. Overall, these results show that estrogen treatment prevents MC38 tumor growth via regulating the tumor immune microenvironment through MC38-EVs.



中文翻译:

雌激素通过逆转细胞外囊泡介导的免疫抑制肿瘤微环境抑制小鼠结肠癌的生长

服用雌激素补充剂的绝经后妇女患晚期结直肠癌的风险较低,但其潜在机制仍不清楚。因此,本研究探讨了雌激素在结直肠癌中的作用。女性患者原位结直肠癌组织中雌激素受体表达水平显着增加,表明其对雌激素敏感。与假手术组相比,去卵巢小鼠中 MC38 肿瘤的生长增强,而在补充 E2 的去卵巢小鼠中则相反。PD-L1 + M2 样巨噬细胞、调节性 T (Treg) 细胞和髓源性抑制细胞 (MDSC) 数量显着增加,细胞毒性 CD8 +数量显着增加在卵巢切除小鼠的 MC38 肿瘤中,T 细胞下降,而在补充 E2 的卵巢切除小鼠中,这一切都逆转了。MC38 细胞衍生的细胞外囊泡 (MC38-EVs) 参与了免疫抑制性肿瘤微环境的建立,而不是来自用 E2 处理的 MC38 细胞的 EVs (E2-MC38-EVs)。E2-MC38-EVs 含有较低的 TGF-β1 水平,并且在体外诱导 Treg 细胞的能力低于 MC38-EVs 。总体而言,这些结果表明雌激素治疗通过 MC38-EVs 调节肿瘤免疫微环境来防止 MC38 肿瘤生长。

更新日期:2021-08-17
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