Three-dimensional invasion of human glioblastoma cells remains unchanged by X-ray and carbon ion irradiation in vitro.
OBJECTIVE
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
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 (γH2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, β1 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 β1 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.
OncoRay--National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Iris
I
Eke
Katja
K
Storch
Ina
I
Kästner
Anne
A
Vehlow
Christina
C
Faethe
Wolfgang
W
Mueller-Klieser
Gisela
G
Taucher-Scholz
Achim
A
Temme
Gabriele
G
Schackert
Nils
N
Cordes
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D001973:Bromodeoxyuridine / Q000032:analysis; D002244:Carbon; D054443:Cell Migration Assays / Q000379:methods; D002465:Cell Movement / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D024042:Collagen Type I; D053903:DNA Breaks, Double-Stranded; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D006657:Histones / Q000032:analysis; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D048670:MAP Kinase Kinase 4 / Q000502:physiology; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000071857:Tumor Suppressor p53-Binding Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D024042:Collagen Type I; C468783:H2AX protein, human; D006657:Histones; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D002244:Carbon; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D001973:Bromodeoxyuridine