Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior
Abstract 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...
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doaj-870adc24b20d4709945c1f69dfd3f0c72020-12-08T00:52:33ZengNature Publishing GroupScientific Reports2045-23222017-08-017111410.1038/s41598-017-07660-4Preventing inflammation inhibits biopsy-mediated changes in tumor cell behaviorMaria Alieva0Andreia S. Margarido1Tamara Wieles2Erik R. Abels3Burcin Colak4Carla Boquetale5Herke Jan Noordmans6Tom J. Snijders7Marike L. Broekman8Jacco van Rheenen9Cancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtCancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtCancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtDepartments of Neurology, Massachusetts General Hospital, Harvard Medical SchoolCancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtCancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtMedical Technology and Clinical Physics, University Medical Center UtrechtDepartment of Neurology & Neurosurgery, Brain Center Rudolf Magnus, University Medical Center UtrechtDepartments of Neurology, Massachusetts General Hospital, Harvard Medical SchoolCancer Genomics Netherlands, Hubrecht Institute-KNAW & University Medical Center UtrechtAbstract 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.https://doi.org/10.1038/s41598-017-07660-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Alieva Andreia S. Margarido Tamara Wieles Erik R. Abels Burcin Colak Carla Boquetale Herke Jan Noordmans Tom J. Snijders Marike L. Broekman Jacco van Rheenen |
spellingShingle |
Maria Alieva Andreia S. Margarido Tamara Wieles Erik R. Abels Burcin Colak Carla Boquetale Herke Jan Noordmans Tom J. Snijders Marike L. Broekman Jacco van Rheenen Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior Scientific Reports |
author_facet |
Maria Alieva Andreia S. Margarido Tamara Wieles Erik R. Abels Burcin Colak Carla Boquetale Herke Jan Noordmans Tom J. Snijders Marike L. Broekman Jacco van Rheenen |
author_sort |
Maria Alieva |
title |
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
title_short |
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
title_full |
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
title_fullStr |
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
title_full_unstemmed |
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
title_sort |
preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-017-07660-4 |
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