Anti-vascular endothelial growth factor therapy-induced glioma invasion is associated with accumulation of Tie2-expressing monocytes.
Anti-vascular endothelial growth factor therapy-induced glioma invasion is associated with accumulation of Tie2-expressing monocytes.
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DOI：
10.18632/oncotarget.1893
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发表时间：
2014-04-30
期刊：
影响因子：
--
通讯作者：
Gomez-Manzano C
中科院分区：
文献类型：
--
作者：
Gabrusiewicz K;Liu D;Cortes-Santiago N;Hossain MB;Conrad CA;Aldape KD;Fuller GN;Marini FC;Alonso MM;Idoate MA;Gilbert MR;Fueyo J;Gomez-Manzano C
将抗血管生成疗法添加到恶性胶质瘤患者可用的少数治疗方法中，是基于这些肿瘤具有高度血管化的事实，以及临床前和临床研究的令人鼓舞的结果。然而，最初对这种治疗有反应的肿瘤总是随着获得高度侵袭性和侵袭性表型而复发。虽然一些髓系人群与这种复发模式有关，但具体的目标人群尚未确定。在这里，我们提出证据表明，在肿瘤侵袭增强的区域，接受抗vegf治疗的小鼠的肿瘤/正常脑界面上，表达tie2的单核/巨噬细胞（TEMs）积累。此外，我们描述了在贝伐单抗治疗后复发的恶性胶质瘤手术标本中tem的存在。我们的研究表明，tem增强胶质瘤细胞的侵袭特性，分泌高水平的明胶酶酶蛋白。因此，在抗vegf治疗的侵袭性肿瘤边缘持续检测到Tie2+MMP9+单核细胞。我们的研究结果表明，存在一个特定的髓/单核细胞亚群，在恶性胶质瘤逃避抗vegf治疗的机制中起着关键作用，因此，在选择抗血管生成治疗的患者中，它构成了联合治疗的新细胞靶点。
The addition of anti-angiogenic therapy to the few treatments available to patients with malignant gliomas was based on the fact that these tumors are highly vascularized and on encouraging results from preclinical and clinical studies. However, tumors that initially respond to this therapy invariably recur with the acquisition of a highly aggressive and invasive phenotype. Although several myeloid populations have been associated to this pattern of recurrence, a specific targetable population has not been yet identified. Here, we present evidence for the accumulation of Tie2-expressing monocytes/macrophages (TEMs) at the tumor/normal brain interface of mice treated with anti-VEGF therapies in regions with heightened tumoral invasion. Furthermore, we describe the presence of TEMs in malignant glioma surgical specimens that recurred after bevacizumab treatment. Our studies showed that TEMs enhanced the invasive properties of glioma cells and secreted high levels of gelatinase enzymatic proteins. Accordingly, Tie2+MMP9+ monocytic cells were consistently detected in the invasive tumor edge upon anti-VEGF therapies. Our results suggest the presence of a specific myeloid/monocytic subpopulation that plays a pivotal role in the mechanism of escape of malignant gliomas from anti-VEGF therapies and therefore constitutes a new cellular target for combination therapies in patients selected for anti-angiogenesis treatment.
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影响因子：
15.9
作者：
Gomez-Manzano, Candelaria;Holash, Jocelyn;Yung, W. K. Alfred
通讯作者：
Yung, W. K. Alfred
影响因子：
15.9
作者：
Dolecek, Therese A.;Propp, Jennifer M.;Kruchko, Carol
通讯作者：
Kruchko, Carol
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1014480108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Keunen, Olivier;Johansson, Mikael;Niclou, Simone P.
通讯作者：
Niclou, Simone P.
影响因子：
--
作者：
Hao NB;Lü MH;Fan YH;Cao YL;Zhang ZR;Yang SM
通讯作者：
Yang SM