Dynamic changes and functions of macrophages and M1/M2 subpopulations during ulcerative colitis-associated carcinogenesis in an AOM/DSS mouse model.
Dynamic changes and functions of macrophages and M1/M2 subpopulations during ulcerative colitis-associated carcinogenesis in an AOM/DSS mouse model.
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AOM/DSS 小鼠模型溃疡性结肠炎相关癌变过程中巨噬细胞和 M1/M2 亚群的动态变化和功能
DOI：
10.3892/mmr.2014.3018
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发表时间：
2015-04
影响因子：
3.4
通讯作者：
Shen S
中科院分区：
文献类型：
--
作者：
Wang W;Li X;Zheng D;Zhang D;Peng X;Zhang X;Ai F;Wang X;Ma J;Xiong W;Li G;Zhou Y;Shen S
众所周知，溃疡性结肠炎（UC）发展为结直肠癌（CRC）的风险很高。巨噬细胞是一种广泛分布的免疫细胞，在UC和CRC中都起着不可或缺的作用。然而，目前对巨噬细胞和M1/M2巨噬细胞亚群在uc相关癌变过程中发生的动态变化知之甚少。本研究的目的是研究uc相关癌变过程中结肠巨噬细胞和M1/M2巨噬细胞亚群的改变。在偶氮氧甲烷/葡聚糖硫酸钠诱导的化学结肠炎相关癌小鼠模型Crj:CD-1 （ICR）小鼠中，研究了uc相关癌变过程中表达水平改变和功能变化。免疫组织化学、流式细胞术、细胞因子检测和基因表达分析的显著证据表明，M2巨噬细胞在结直肠癌的发生、促进和转移中起着关键作用。M2巨噬细胞与促炎轴和抗炎轴失衡以及迁移/侵袭相关因子的异常增强有关。在癌症和转移的发展过程中，M1巨噬细胞出现了类似于M2极化巨噬细胞的功能变化，而没有表型变化。本研究结果提示M2巨噬细胞在uc相关癌变过程中具有促瘤作用。此外，在癌变和转移过程中，M1巨噬细胞也发生了类似的功能变化，但没有极化改变。
The high risk of developing colorectal carcinoma (CRC), from ulcerative colitis (UC), is well known. Macrophages are widely distributed immune cells that have an indispensable role in UC, as well as in CRC. However, little is currently known about the dynamic changes that occur in macrophage and M1/M2 macrophage subpopulations, during UC-associated carcinogenesis. The aim of the present study was to investigate the alteration of colorectal macrophages and M1/M2 macrophage subpopulations during UC-associated carcinogenesis. Both expression level alterations and functional changes were determined during UC-associated carcinogenesis in an azoxymethane/dextran sodium sulfate-induced chemically colitis-associated carcinoma mouse model of Crj:CD-1 (ICR) mice. Notable evidence from immunohistochemistry, flow cytometry, cytokine detection, and gene expression analyses demonstrated that M2 macrophages have a critical role in CRC initiation, promotion, and metastasis. M2 macrophages are associated with unbalanced pro-inflammatory and anti-inflammatory axes and aberrant enhancement of migration/invasion-associated factors. Functional changes, similar to M2 polarized macrophages, were shown to occur in the M1 macrophages, without phenotypical changes, during the development of carcinoma and metastasis. The results of the present study suggest that M2 macrophages have a pro-tumor role during UC-associated carcinogenesis. Furthermore, similar functional changes occurred in the M1 macrophages, without polarization alterations, during carcinogenesis and metastasis.
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影响因子：
15.9
作者：
Imtiyaz, Hongxia Z.;Williams, Emily P.;Simon, M. Celeste
通讯作者：
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3.1
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影响因子：
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作者：
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通讯作者：
Darzi, Ara
影响因子：
3.1
作者：
Martinez, Fernando Oneissi;Sica, Antonio;Locati, Massimo
通讯作者：
Locati, Massimo