Adipose tissue macrophage polarization by intermittent hypoxia in a mouse model of OSA: Effect of tumor microenvironment
Adipose tissue macrophage polarization by intermittent hypoxia in a mouse model of OSA: Effect of tumor microenvironment
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DOI：
10.1016/j.canlet.2015.03.010
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发表时间：
2015-06-01
期刊：
影响因子：
9.7
通讯作者：
Gozal, David
中科院分区：
文献类型：
--
作者：
Almendros, Isaac;Gileles-Hillel, Alex;Gozal, David
间歇性缺氧（IH）-诱导肿瘤相关巨噬细胞（TAM）的改变，与不良癌症结局相关，如患有睡眠呼吸暂停的患者所报告的那样。脂肪组织（AT）和骨髓（BM）来源的细胞是巨噬细胞浸润恶性肿瘤的推断来源。本研究采用同系小鼠实体瘤模型（TC 1），研究了IH对同侧和对侧AT的表型影响及TAM的来源。巨噬细胞的含量，表型和组织来源进行了评估，在肿瘤，同侧和对侧AT。IH诱导TAM肿瘤浸润增加了2.2倍。然而，出现了肿瘤同侧和对侧AT的差异反应：IH增加了对侧AT中优先M1巨噬细胞的浸润，而同侧AT中出现了巨噬细胞的减少，主要由M2表型组成。这些变化是伴随着互惠增加居民和BM衍生的TAM在tumor. IH诱导的表型改变AT巨噬细胞周围的肿瘤和肿瘤内的浸润增加可能有助于加速肿瘤进展与IH。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Intermittent hypoxia (IH)-induces alterations in tumor-associated macrophages (TAMs) that are associated with adverse cancer outcomes, as reported in patients suffering from sleep apnea. Adipose tissues (AT) and bone-marrow (BM)-derived cells are the inferred sources of macrophages infiltrating malignant tumors. Here, the sources of TAMs and the phenotypic changes induced by IH in the ipsilateral and contralateral AT were investigated by using a syngeneic murine solid tumor model (TC1).C57/B6 male mice were exposed to either IH or room air (RA) for 6 weeks, With TC1 cells being inoculated in the 2nd week. Macrophage content, phenotype and tissue origin were assessed in tumors, and ipsilateral and contralateral AT.IH induced a similar to 2.2-fold increase in TAM tumor infiltration. However, differential responses in the tumor ipsilateral and contralateral AT emerged: IH increased infiltration of preferentially M1 macrophages in contralateral AT, while reductions in macrophages emerged in ipsilateral AT and primarily consisted of the M2 phenotype. These changes were accompanied by reciprocal increases in resident and BM-derived TAMs in the tumor.IH-induced phenotypic alterations in AT macrophages surrounding the tumor and their increased infiltration within the tumor may contribute to the accelerated tumor progression associated with IH. (C) 2015 Elsevier Ireland Ltd. All rights reserved.