Role of Macrophage Migration Inhibitory Factor in Primary Glioblastoma Multiforme Cells
Role of Macrophage Migration Inhibitory Factor in Primary Glioblastoma Multiforme Cells
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DOI：
10.1002/jnr.22595
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发表时间：
2011-05-01
影响因子：
4.2
通讯作者：
Bacher, Michael
中科院分区：
文献类型：
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作者：
Baron, Nina;Deuster, Oliver;Bacher, Michael
巨噬细胞移动抑制因子（MIF）是一种在许多肿瘤中过表达的蛋白质，如结肠癌和前列腺癌、黑色素瘤和多形性胶质母细胞瘤（GBM）。在其作为细胞因子的功能中，MIF诱导血管生成，促进细胞周期进程，并抑制凋亡。近年来，MIF的分子信号转导已被明确：MIF被发现是CD 74/CD 44受体复合物的配体，并激活ERK 1/2 MAPK级联反应。此外，MIF与趋化因子受体CXCR 2和CXCR 4结合。这影响整合素依赖性白细胞停滞并介导白细胞趋化性。最近的工作描述了一个更清晰的作用，MIF在GBM肿瘤细胞系。目前的研究使用人类原代GBM细胞。我们发现，用MIF的D-多巴色素互变异构酶位点的抑制剂ISO-1抑制MIF，以剂量依赖性方式降低原代GBM细胞的生长速率，此外ISO-1在体外增加MIF及其受体CD 74、CXCR 2和CXCR 4的蛋白表达，但降低CD 44的表达。此外，缺氧作为细胞应激源增加了原代GBM细胞中MIF的蛋白表达。这些结果强调了MIF在GBM中的重要性，并表明MIF及其受体可能是治疗恶性胶质瘤的有希望的靶点。(C)2011 Wiley-Liss，Inc.
Macrophage migration inhibitory factor (MIF) is a protein that is overexpressed in many tumors, such as colon and prostate cancer, melanoma, and glioblastoma multi-forme (GBM). In its function as a cytokine, MIF induces angiogenesis, promotes cell cycle progression, and inhibits apoptosis. Recently, the molecular signal transduction has been specified: MIF has been found to be a ligand to the CD74/CD44-receptor complex and to activate the ERK1/2 MAPK cascade. In addition MIF binds to the chemokine receptors CXCR2 and CXCR4. This effects an integrin-dependent leukocyte arrest and mediates leukocyte chemotaxis. Recent work has described a clearer role of MIF in GBM tumor cell lines. The current study used human primary GBM cells. We show that inhibition of MIF with ISO-1, an inhibitor of the D-dopachrome tautomerase site of MIF, reduced the growth rate of primary GBM cells in a dose-dependent manner, and in addition ISO-1 increased protein expression of MIF and its receptors CD74, CXCR2, and CXCR4 in vitro but decreased expression of CD44. Furthermore, hypoxia as cell stressor increases the protein expression of MIF in primary GBM cells. These results underscore the importance of MIF in GBM and show that MIF and its receptors may be a promising target for the treatment of malignant gliomas. (C) 2011 Wiley-Liss, Inc.