Carbon ion radiation inhibits glioma and endothelial cell migration induced by secreted VEGF

Yang Liu; Yuanyuan Liu; Chao Sun; Lu Gan; Luwei Zhang; Aihong Mao; Yuting Du; Rong Zhou; Hong Zhang

doi:10.1371/journal.pone.0098448

Carbon ion radiation inhibits glioma and endothelial cell migration induced by secreted VEGF

PLoS One. 2014 Jun 3;9(6):e98448. doi: 10.1371/journal.pone.0098448. eCollection 2014.

Authors

Yang Liu¹, Yuanyuan Liu¹, Chao Sun¹, Lu Gan¹, Luwei Zhang¹, Aihong Mao², Yuting Du³, Rong Zhou¹, Hong Zhang¹

Affiliations

¹ Department of Radiation Medicine, Institute of Modern physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, China.
² Department of Radiation Medicine, Institute of Modern physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou, China; Graduate School of Chinese Academy of Sciences, Beijing, China.
³ Lanzhou University, Hospital of Stomatology, Lanzhou, China.

Abstract

This study evaluated the effects of carbon ion and X-ray radiation and the tumor microenvironment on the migration of glioma and endothelial cells, a key process in tumorigenesis and angiogenesis during cancer progression. C6 glioma and human microvascular endothelial cells were treated with conditioned medium from cultures of glioma cells irradiated at a range of doses and the migration of both cell types, tube formation by endothelial cells, as well as the expression and secretion of migration-related proteins were evaluated. Exposure to X-ray radiation-conditioned medium induced dose-dependent increases in cell migration and tube formation, which were accompanied by an upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9 expression. However, glioma cells treated with conditioned medium of cells irradiated at a carbon ion dose of 4.0 Gy showed a marked decrease in migratory potential and VEGF secretion relative to non-irradiated cells. The application of recombinant VEGF165 stimulated migration in glioma and endothelial cells, which was associated with increased FAK phosphorylation at Tyr861, suggesting that the suppression of cell migration by carbon ion radiation could be via VEGF-activated FAK signaling. Taken together, these findings indicate that carbon ion may be superior to X-ray radiation for inhibiting tumorigenesis and angiogenesis through modulation of VEGF level in the glioma microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Neoplasms / enzymology
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Carbon / chemistry*
Cell Line, Tumor
Cell Migration Assays
Cell Movement / drug effects
Cell Movement / radiation effects*
Collagen / pharmacology
Culture Media, Conditioned / pharmacology
Drug Combinations
Endothelial Cells / drug effects
Endothelial Cells / metabolism*
Endothelial Cells / pathology
Gene Expression Regulation / drug effects
Gene Expression Regulation / radiation effects
Glioma / enzymology
Glioma / metabolism*
Glioma / pathology*
Humans
Ions
L-Lactate Dehydrogenase / metabolism
Laminin / pharmacology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Neovascularization, Physiologic / drug effects
Neovascularization, Physiologic / radiation effects
Proteoglycans / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism*

Substances

Culture Media, Conditioned
Drug Combinations
Ions
Laminin
Proteoglycans
RNA, Messenger
Vascular Endothelial Growth Factor A
matrigel
Carbon
Collagen
L-Lactate Dehydrogenase
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9

Grants and funding

This work was supported by grants from the National Basic Research Program of China (2010CB834202), The National Natural Science Foundation of China (11205214 and 11305224), the Scientific Technology Research Projects of Gansu Province (0702NKDA045, 0806RJYA020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.