Tumor hypoxia enhances Non-Small Cell Lung Cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling.
Tumor hypoxia enhances Non-Small Cell Lung Cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling.
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DOI：
10.18632/oncotarget.1856
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发表时间：
2014-10-30
期刊：
影响因子：
--
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Zhang J;Cao J;Ma S;Dong R;Meng W;Ying M;Weng Q;Chen Z;Ma J;Fang Q;He Q;Yang B
缺氧是大多数人类肿瘤中的常见现象，并且已被证明在肿瘤进展中起重要作用。然而，目前尚不清楚低氧对巨噬细胞的作用是否是低氧介导的肿瘤侵袭行为的主要驱动力。在本研究中，我们观察到高密度的M2巨噬细胞与腺癌非小细胞肺癌（NSCLC）患者的转移有关。应用体内缺氧模型，结果表明间歇性缺氧明显促进刘易斯肺癌（LLC）的转移，并伴有更多的CD 209+巨噬细胞浸润于原发肿瘤组织。更有趣的是，通过使巨噬细胞极化远离M1-至肿瘤促进M2样表型，缺氧和IL-6协同增强LLC在体外和体内的转移。此外，我们还表明，偏斜的巨噬细胞M2极化缺氧依赖于ERK信号的激活。总的来说，这些观察揭示了一个新的肿瘤缺氧的概念，涉及巨噬细胞表型的转变，并提供直接的证据，肺癌干预，通过调节巨噬细胞的表型。
Hypoxia is a common phenomenon occurring in the majority of human tumors and has been proved to play an important role in tumor progression. However, it remains unclear that whether the action of hypoxia on macrophages is a main driving force of hypoxia-mediated aggressive tumor behaviors. In the present study, we observe that high density of M2 macrophages is associated with metastasis in adenocarcinoma Non-Small Cell Lung Cancer (NSCLC) patients. By applying the in vivo hypoxia model, the results suggest that intermittent hypoxia significantly promotes the metastasis of Lewis lung carcinoma (LLC), accompanied with more CD209+ macrophages infiltrated in primary tumor tissue. More intriguingly, by skewing macrophages polarization away from the M1- to a tumor-promoting M2-like phenotype, hypoxia and IL-6 cooperate to enhance the LLC metastasis both in vitro and in vivo. In addition, we also demonstrate that skewing of macrophage M2 polarization by hypoxia relies substantially on activation of ERK signaling. Collectively, these observations unveil a novel tumor hypoxia concept involving the macrophage phenotype shift and provide direct evidence for lung cancer intervention through modulating the phenotype of macrophages.
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影响因子：
20.3
作者：
Liu, W;Guo, M;Chen, GQ
通讯作者：
Chen, GQ
影响因子：
4.4
作者：
Acosta-Iborra, Barbara;Elorza, Ainara;Landazuri, Manuel O.
通讯作者：
Landazuri, Manuel O.
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
20.3
作者：
Duluc, Dorothee;Delneste, Yves;Jeannin, Pascale
通讯作者：
Jeannin, Pascale
DOI：
10.1073/pnas.0909353106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Lee, KangAe;Zhang, Huafeng;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.