Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

TY - JOUR

T1 - Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

AU - Alieva, Maria

AU - Margarido, Andreia S

AU - Wieles, Tamara

AU - Abels, Erik R

AU - Colak, Burcin

AU - Boquetale, Carla

AU - Jan Noordmans, Herke

AU - Snijders, Tom J

AU - Broekman, Marike L D

AU - van Rheenen, Jacco

PY - 2017/8/8

Y1 - 2017/8/8

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41598-017-07660-4

DO - 10.1038/s41598-017-07660-4

M3 - Article

C2 - 28790339

SN - 2045-2322

VL - 7

SP - 7529

JO - Scientific Reports

JF - Scientific Reports

IS - 1

ER -