Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

被引:51
作者
Alieva, Maria [1 ,2 ]
Margarido, Andreia S. [1 ,2 ]
Wieles, Tamara [1 ,2 ]
Abels, Erik R. [3 ]
Colak, Burcin [1 ,2 ]
Boquetale, Carla [1 ,2 ]
Noordmans, Herke Jan [4 ]
Snijders, Tom J. [5 ]
Broekman, Marike L. [3 ,5 ]
van Rheenen, Jacco [1 ,2 ]
机构
[1] Hubrecht Inst KNAW, Canc Genom Netherlands, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands
[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Boston, MA 02129 USA
[4] Univ Med Ctr Utrecht, Dept Med Technol & Clin Phys, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands
[5] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands
基金
欧洲研究理事会; 欧盟地平线“2020”;
关键词
NEEDLE-BIOPSY; CANCER; MONOCYTES; GLIOMA; MACROPHAGES; DEXAMETHASONE; GLIOBLASTOMA; RECRUITMENT; METASTASIS; THERAPY;
D O I
10.1038/s41598-017-07660-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures.
引用
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页数:14
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