Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands.
Departments of Neurology, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Boston, MA, 02129, USA.
Sci Rep. 2017 Aug 8;7(1):7529. doi: 10.1038/s41598-017-07660-4.
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.
虽然活检和肿瘤切除对胶质母细胞瘤（GBM）具有预后益处，但也有人提出了潜在的负面影响。在这里，我们通过对患者的回顾性研究和对小鼠的活体成像，确定了其中的一些负面影响，包括对未切除肿瘤细胞的增殖和迁移的刺激，并提供了一种预防这些不利影响的策略。通过重复高分辨率活体显微镜检查，我们表明 GBM 中的活检样损伤通过趋化因子（C-C 基序）配体 2（CCL-2）依赖性招募巨噬细胞来诱导肿瘤细胞的迁移和增殖。阻断巨噬细胞的募集或给予地塞米松（一种常用于预防 GBM 患者脑水肿的糖皮质激素），可抑制在小鼠和多灶性 GBM 患者中观察到的活检后的炎症反应和随后的肿瘤生长。总之，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。
