Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation.
Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation.
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DOI：
10.1016/j.yexmp.2009.01.001
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发表时间：
2009-06
影响因子：
3.6
通讯作者：
Mitchell, Robert A.
中科院分区：
文献类型：
--
作者：
Rendon, Beatriz E.;Willer, Sharon S.;Zundel, Wayne;Mitchell, Robert A.
自从 20 世纪 60 年代中期首次报道其活性以来，巨噬细胞迁移抑制因子 (MIF) 已从调节单核细胞运动的细胞因子活性转变为大量细胞和生物过程的多效性调节剂。近年来的研究表明，MIF 在几个不同层面上促进恶性疾病的进展。癌症患者中循环和细胞内 MIF 蛋白水平均升高，据报道 MIF 表达与分期、转移扩散和无病生存相关。此外，MIF 表达与血管生成生长因子表达、微血管密度和肿瘤相关新血管形成呈正相关。并非巧合的是，MIF 最近被证明可以通过促进缺氧诱导的 HIF-1α 稳定来促进肿瘤缺氧适应。有趣的是，缺氧是 MIF 表达和分泌的强调节因子，这表明缺氧诱导的 MIF 在人类恶性肿瘤中充当缺氧和常氧相关血管生成生长因子表达的放大因子。综合起来，这些发现表明 MIF 过度表达有助于肿瘤的缺氧适应，进而有助于治疗反应和疾病预后。本综述总结了有关 MIF 对肿瘤相关血管生成生长因子表达、新生血管形成和缺氧适应的贡献的最新文献。我们还将回顾最近旨在识别和使用 MIF 小分子拮抗剂作为癌症治疗新方法的努力。
Since its activity was first reported in the mid-1960s, macrophage migration inhibitory factor (MIF) has gone from a cytokine activity modulating monocyte motility to a pleiotropic regulator of a vast array of cellular and biological processes. Studies in recent years suggest that MIF contributes to malignant disease progression on several different levels. Both circulating and intracellular MIF protein levels are elevated in cancer patients and MIF expression reportedly correlates with stage, metastatic spread and disease-free survival. Additionally, MIF expression positively correlates with angiogenic growth factor expression, microvessel density and tumor-associated neovascularization. Not coincidentally, MIF has recently been shown to contribute to tumoral hypoxic adaptation by promoting hypoxia-induced HIF-1α stabilization. Intriguingly, hypoxia is a strong regulator of MIF expression and secretion, suggesting that hypoxia-induced MIF acts as an amplifying factor for both hypoxia and normoxia-associated angiogenic growth factor expression in human malignancies. Combined, these findings suggest that MIF overexpression contributes to tumoral hypoxic adaptation and, by extension, therapeutic responsiveness and disease prognosis. This review summarizes recent literature on the contributions of MIF to tumor-associated angiogenic growth factor expression, neovascularization and hypoxic adaptation. We also will review recent efforts aimed at identifying and employing small-molecule antagonists of MIF as a novel approach to cancer therapeutics.
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DOI：
10.1084/jem.190.10.1375
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hudson JD;Shoaibi MA;Maestro R;Carnero A;Hannon GJ;Beach DH
通讯作者：
Beach DH
DOI：
10.4049/jimmunol.181.4.2330
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Coleman AM;Rendon BE;Zhao M;Qian MW;Bucala R;Xin D;Mitchell RA
通讯作者：
Mitchell RA
影响因子：
30.5
作者：
de Jong, YP;Abadia-Molina, AC;Terhorst, C
通讯作者：
Terhorst, C
影响因子：
4.4
作者：
Kevill, Katharine A.;Bhandari, Vineet;Bucala, Richard J.
通讯作者：
Bucala, Richard J.
影响因子：
10.5
作者：
Bemis, L;Chan, DA;Zundel, W
通讯作者：
Zundel, W