Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior
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DOI：
10.1038/s41598-017-07660-4
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发表时间：
2017-08-08
影响因子：
4.6
通讯作者：
van Rheenen, Jacco
中科院分区：
文献类型：
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作者：
Alieva, Maria;Margarido, Andreia S.;van Rheenen, Jacco
虽然活检和肿瘤切除术对胶质母细胞瘤（GBM）有治疗益处，但也有潜在的负面影响。在这里，通过对患者的回顾性研究和小鼠的活体成像，我们确定了其中一些负面影响，包括刺激未切除肿瘤细胞的增殖和迁移，并提供了预防这些不良反应的策略。通过重复的高分辨率活体显微镜检查，我们发现GBM中的活检样损伤通过趋化因子（C-C基序）配体2（CCL-2）依赖的巨噬细胞募集诱导肿瘤细胞的迁移和增殖。阻断巨噬细胞募集或给予地塞米松（一种常用的糖皮质激素，用于预防GBM患者的脑水肿）抑制了小鼠和多灶性GBM患者活检时观察到的炎症反应和随后的肿瘤生长。综上所述，我们的研究表明，抑制CCL-2依赖性巨噬细胞募集可能会进一步增加手术和活检程序的临床获益。
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.