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

Liu Y, Liu Y, Sun C, Gan L, Zhang L, Mao A, Du Y, Zhou R, Zhang H - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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VEGF and MMP-2 and -9 protein concentration in conditioned media from cultures of irradiated tumor cells.C6 glioma cell culture supernatant was collected 24-ray irradiation, and protein levels were measured by ELISA. Data represent the mean ± standard error of the mean from six independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs. controls (0 Gy).
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pone-0098448-g004: VEGF and MMP-2 and -9 protein concentration in conditioned media from cultures of irradiated tumor cells.C6 glioma cell culture supernatant was collected 24-ray irradiation, and protein levels were measured by ELISA. Data represent the mean ± standard error of the mean from six independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs. controls (0 Gy).

Mentions: VEGF and MMP-2 and -9 levels in conditioned media from cultures of glioma cells treated with varying doses of X-ray or carbon ion radiation were evaluated by ELISA. All three proteins were present at higher levels in the media of X-ray-irradiated cultures than in unirradiated cell culture medium (Fig. 4). There were no differences in the secretion of MMP-2 and -9 between carbon ion-irradiated cells and controls; however, VEGF concentration was 17.5% lower in the medium of cells irradiated with carbon ion at 4.0 Gy compared to the control culture (Fig. 4A).


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

Liu Y, Liu Y, Sun C, Gan L, Zhang L, Mao A, Du Y, Zhou R, Zhang H - PLoS ONE (2014)

VEGF and MMP-2 and -9 protein concentration in conditioned media from cultures of irradiated tumor cells.C6 glioma cell culture supernatant was collected 24-ray irradiation, and protein levels were measured by ELISA. Data represent the mean ± standard error of the mean from six independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs. controls (0 Gy).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043910&req=5

pone-0098448-g004: VEGF and MMP-2 and -9 protein concentration in conditioned media from cultures of irradiated tumor cells.C6 glioma cell culture supernatant was collected 24-ray irradiation, and protein levels were measured by ELISA. Data represent the mean ± standard error of the mean from six independent experiments. *P<0.05, **P<0.01, ***P<0.001 vs. controls (0 Gy).
Mentions: VEGF and MMP-2 and -9 levels in conditioned media from cultures of glioma cells treated with varying doses of X-ray or carbon ion radiation were evaluated by ELISA. All three proteins were present at higher levels in the media of X-ray-irradiated cultures than in unirradiated cell culture medium (Fig. 4). There were no differences in the secretion of MMP-2 and -9 between carbon ion-irradiated cells and controls; however, VEGF concentration was 17.5% lower in the medium of cells irradiated with carbon ion at 4.0 Gy compared to the control culture (Fig. 4A).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus