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Title: Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro

Abstract

Purpose: Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions. Methods and Materials: Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks ({gamma}H2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, {beta}1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation. Results: Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the {beta}1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion. Conclusions: These findings indicate that X-rays and carbonmore » ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.« less

Authors:
; ; ;  [1]; ;  [2];  [3]; ;  [4];  [1];  [5]
  1. OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)
  2. Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz (Germany)
  3. Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, Darmstadt (Germany)
  4. Section of Experimental Neurosurgery/Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)
  5. (Germany)
Publication Date:
OSTI Identifier:
22149650
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARBON IONS; CELL PROLIFERATION; COLLAGEN; COMBINED THERAPY; DEOXYURIDINE; DNA; GLIOMAS; IN VITRO; IRRADIATION; PATIENTS; STRAND BREAKS; X RADIATION

Citation Formats

Eke, Iris, Storch, Katja, Kaestner, Ina, Vehlow, Anne, Faethe, Christina, Mueller-Klieser, Wolfgang, Taucher-Scholz, Gisela, Temme, Achim, Schackert, Gabriele, Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de, and Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden. Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2012.06.012.
Eke, Iris, Storch, Katja, Kaestner, Ina, Vehlow, Anne, Faethe, Christina, Mueller-Klieser, Wolfgang, Taucher-Scholz, Gisela, Temme, Achim, Schackert, Gabriele, Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de, & Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden. Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro. United States. doi:10.1016/J.IJROBP.2012.06.012.
Eke, Iris, Storch, Katja, Kaestner, Ina, Vehlow, Anne, Faethe, Christina, Mueller-Klieser, Wolfgang, Taucher-Scholz, Gisela, Temme, Achim, Schackert, Gabriele, Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de, and Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden. Thu . "Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro". United States. doi:10.1016/J.IJROBP.2012.06.012.
@article{osti_22149650,
title = {Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro},
author = {Eke, Iris and Storch, Katja and Kaestner, Ina and Vehlow, Anne and Faethe, Christina and Mueller-Klieser, Wolfgang and Taucher-Scholz, Gisela and Temme, Achim and Schackert, Gabriele and Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de and Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden},
abstractNote = {Purpose: Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions. Methods and Materials: Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks ({gamma}H2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, {beta}1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation. Results: Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the {beta}1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion. Conclusions: These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.},
doi = {10.1016/J.IJROBP.2012.06.012},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 4,
volume = 84,
place = {United States},
year = {2012},
month = {11}
}