Irradiated normal brain promotes invasion of glioblastoma through vascular endothelial growth and stromal cell-derived factor 1α.
The significance of irradiated normal brain volume in glioma recurrence is usually ignored by radiotherapists. The whole-brain irradiation (WBI) of 15 Gy in three fractions was delivered to C57BL/6 mice before implantation of GL261 glioma cells. The changes in vascular endothelial growth (VEGF) and stromal cell-derived factor 1α (SDF-1α) after WBI were evaluated by real-time RT-PCR and immunohistochemistry. Cell invasion assays were performed to study the effects of VEGF and SDF-1α. The levels of VEGF and SDF-1α in normal brain tissues increased after 15 Gy WBI. The WBI before tumor implantation significantly increased the invasive ability of GL261 cells. VEGF and SDF-1α could promote invasion of GL261 cells even after high-dose irradiation. The combination of irradiation and inhibitors such as AMD3100 may prevent irradiation-stimulated dissemination of glioma cells.
Department of Radiotherapy, Qilu Hospital, Shandong University, 44 Wenhuaxi Road, Jinan,Shandong, China.
Wei
W
Zhou
Yangyang
Y
Xu
Ge
G
Gao
Zheng
Z
Jiang
Xingang
X
Li
D000818:Animals; D001596:Benzylamines; D001921:Brain / Q000528:radiation effects*; D001923:Brain Chemistry / Q000528:radiation effects; D001932:Brain Neoplasms / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000502:physiology*; D000080027:Cyclams; D016207:Cytokines / Q000378:metabolism; D005720:Gamma Rays; D005909:Glioblastoma / Q000473:pathology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C088327:plerixafor