Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model.
Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model.
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在基于 MAFIA 的神经胶质瘤模型中，巨噬细胞消融可减少 M2 样细胞群并危及肿瘤生长。
DOI：
10.1016/j.neo.2015.03.003
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发表时间：
2015-04
期刊：
影响因子：
4.8
通讯作者：
Gomez-Manzano, Candelaria
中科院分区：
文献类型：
--
作者：
Gabrusiewicz, Konrad;Hossain, Mohammad B.;Cortes-Santiago, Nahir;Fan, Xuejun;Kaminska, Bozena;Marini, Frank C.;Fueyo, Juan;Gomez-Manzano, Candelaria
单核细胞/巨噬细胞是胶质瘤微环境的重要组成部分。然而，由于缺乏研究这些细胞固有复杂性的模型，了解它们的多样性和可塑性是最具挑战性的研究领域之一。在此，我们通过使用转基因模型分析了单核/巨噬细胞在胶质瘤生长中的作用，该模型允许有条件地消融这些细胞群。我们使用含gl261的CSF-1R-GFP +巨噬细胞fas诱导凋亡（MAFIA）转基因小鼠建立脑胶质瘤模型。通过暴露于二聚体AP20187实现条件巨噬细胞消融。双免疫荧光用于表征肿瘤生长期间和条件消融后的M1和m2样单核/巨噬细胞。在胶质瘤生长过程中，单核细胞/巨噬细胞主要由M2巨噬细胞组成。巨噬细胞的条件性时间消耗减少了GFP+细胞的数量，主要针对M2极化细胞的再生，并改变了M1样单核细胞/巨噬细胞的外观，这表明M1/M2巨噬细胞平衡发生了变化。有趣的是，与对照组相比，巨噬细胞缺失小鼠的肿瘤有丝分裂指数、微血管密度和肿瘤生长均较低。这些结果证明了在体内研究巨噬细胞在胶质瘤中的作用和表型的可能性，并提示CSF-1R+群体的短暂耗竭会影响这些细胞的重建表型池，最终抑制肿瘤生长。黑手党模型在定义巨噬细胞在胶质瘤中的作用方面提供了急需的进展。
Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages in glioma growth by using a transgenic model that allows for conditional ablation of this cell population. We modeled glioma using intracranial GL261-bearing CSF-1R–GFP+ macrophage Fas-induced apoptosis (MAFIA) transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used to characterize M1- and M2-like monocytes/macrophages during tumor growth and after conditional ablation. During glioma growth, the monocyte/macrophage population consisted predominantly of M2 macrophages. Conditional temporal depletion of macrophages reduced the number of GFP+ cells, targeting mainly the repopulation of M2-polarized cells, and altered the appearance of M1-like monocytes/macrophages, which suggested a shift in the M1/M2 macrophage balance. Of interest, compared with control-treated mice, macrophage-depleted mice had a lower tumor mitotic index, microvascular density, and reduced tumor growth. These results demonstrated the possibility of studying in vivo the role and phenotype of macrophages in gliomas and suggested that transitory depletion of CSF-1R+ population influences the reconstitutive phenotypic pool of these cells, ultimately suppressing tumor growth. The MAFIA model provides a much needed advance in defining the role of macrophages in gliomas.
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影响因子：
4.2
作者：
Clifford, A. B.;Elnaggar, A. M.;O'Neill, K.
通讯作者：
O'Neill, K.
影响因子：
3.3
作者：
Steel CD;Kim WK;Sanford LD;Wellman LL;Burnett S;Van Rooijen N;Ciavarra RP
通讯作者：
Ciavarra RP
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.2
作者：
Burnett, SH;Beus, BJ;Cohen, DA
通讯作者：
Cohen, DA
影响因子：
3.9
作者：
Leten, Cindy;Struys, Tom;Himmelreich, Uwe
通讯作者：
Himmelreich, Uwe