Intrahepatic cholangiocarcinoma induced M2-polarized tumor-associated macrophages facilitate tumor growth and invasiveness.
Intrahepatic cholangiocarcinoma induced M2-polarized tumor-associated macrophages facilitate tumor growth and invasiveness.
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肝内胆管癌诱导的 M2 极化肿瘤相关巨噬细胞促进肿瘤生长和侵袭
DOI：
10.1186/s12935-020-01687-w
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发表时间：
2020-12-07
影响因子：
5.8
通讯作者：
Hong J
中科院分区：
文献类型：
--
作者：
Yuan H;Lin Z;Liu Y;Jiang Y;Liu K;Tu M;Yao N;Qu C;Hong J
研究背景M2极化的肿瘤相关巨噬细胞(M2-TAMs)与多种肿瘤的进展有关，包括肝内胆管细胞癌(ICC)。然而，M2巨噬细胞与ICC之间的相互作用及其机制尚不完全清楚。本研究旨在阐明M2巨噬细胞是否促进ICC恶变及其机制。方法采用两种进展性ICC小鼠模型，观察不同巨噬细胞群和表型的变化。此外，我们还评估了48例人ICC和15例正常肝脏标本中M2巨噬细胞的浸润情况。结果两种模型小鼠肝内胆管组织中M2巨噬细胞数量均明显高于正常胆管组织。M2巨噬细胞在瘤周较瘤内区和正常肝脏明显增多(p<； )。诱导巨噬细胞向M2-表型分化，并与M2-M_2巨噬细胞共同培养，促进细胞的增殖、侵袭和上皮-间充质转化。在机制上，M2-衍生的IL-10通过STAT3信号通路促进肝癌细胞的恶性转化。此外，阻断IL-10/STAT3信号通路部分挽救了M2巨噬细胞对ICC的作用。结论ICC诱导的M2极化巨噬细胞通过IL-10/STAT3诱导的EMT促进肿瘤生长和侵袭，可能成为ICC的潜在治疗靶点。
BackgroundM2-polarized tumor-associated macrophages (M2-TAMs) have been shown to correlate with the progression of various cancers, including intrahepatic cholangiocarcinoma (ICC). However, the interactions and mechanism between M2 macrophages and ICC are not completely clear. We aimed to clarify whether M2 macrophages promote the malignancy of ICC and its mechanism.MethodsTwo progressive murine models of ICC were used to evaluate the alterations in different macrophage populations and phenotypes. Furthermore, we assessed M2 macrophage infiltration in 48 human ICC and 15 normal liver samples. The protumor functions and the underlying molecular mechanisms of M2 macrophages in ICC were investigated in an in vitro coculture system.ResultsWe found that the number of M2 macrophages was significantly higher in ICC tissues than in normal bile ducts in the two murine models. M2 macrophage infiltration was highly increased in peritumoral compared with intratumoral regions and normal liver (p< 0.01). ICC cells induced macrophages to differentiate into the M2-TAM phenotype, and coculture with these M2 macrophages promoted ICC cell proliferation, invasion and epithelial–mesenchymal transition (EMT) in vitro. Mechanistically, M2-TAM-derived IL-10 promoted the malignant properties of ICC cells through STAT3 signaling. Furthermore, blockade of IL-10/STAT3 signaling partly rescued the effects of M2 macrophages on ICC.ConclusionOur results indicated that M2-polarized macrophages induced by ICC promote tumor growth and invasiveness through IL-10/STAT3-induced EMT and might be a potential therapeutic target for ICC.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6.6
作者：
Suarez-Carmona M;Lesage J;Cataldo D;Gilles C
通讯作者：
Gilles C
影响因子：
2.3
作者：
Guro, Hanisah;Kim, Jin Won;Han, Ho-Seong
通讯作者：
Han, Ho-Seong
影响因子：
50.3
作者：
Rolny, Charlotte;Mazzone, Massimiliano;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
DOI：
10.1634/theoncologist.2015-0446
发表时间：
2016-05
期刊：
The oncologist
影响因子：
--
作者：
Saha SK;Zhu AX;Fuchs CS;Brooks GA
通讯作者：
Brooks GA