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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-induced endothelial and glioma cell migration.A. HMEC-1 and B. C6 glioma cells were cultured in media from cultures of carbon ion-irradiated glioma cells supplemented with VEGF165 (50 ng/ml). C. Quantification of migrating cells. Data represent the mean ± standard error of the mean from at least three independent experiments. D. Expression of phosphorylated FAK (Y861) in cells after addition of VEGF165, as determined by western blotting.
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pone-0098448-g006: VEGF-induced endothelial and glioma cell migration.A. HMEC-1 and B. C6 glioma cells were cultured in media from cultures of carbon ion-irradiated glioma cells supplemented with VEGF165 (50 ng/ml). C. Quantification of migrating cells. Data represent the mean ± standard error of the mean from at least three independent experiments. D. Expression of phosphorylated FAK (Y861) in cells after addition of VEGF165, as determined by western blotting.

Mentions: To examine the functional significance of altered VEGF level in the culture medium of irradiated tumor cells, conditioned media were supplemented with recombinant VEGF165 (50 ng/ml) and the effect on cell migration was evaluated by wound-healing assay. The migration of HMEC-1 and C6 glioma cells was increased by 1.31- and 1.58-fold, respectively, in the presence of VEGF165 (Fig. 6C). Moreover, after a 4 h incubation in media from carbon ion-irradiated cell cultures supplemented with VEGF165, both cell types showed increases in levels of phosphorylated FAK (Y861) (Fig. 6D).


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-induced endothelial and glioma cell migration.A. HMEC-1 and B. C6 glioma cells were cultured in media from cultures of carbon ion-irradiated glioma cells supplemented with VEGF165 (50 ng/ml). C. Quantification of migrating cells. Data represent the mean ± standard error of the mean from at least three independent experiments. D. Expression of phosphorylated FAK (Y861) in cells after addition of VEGF165, as determined by western blotting.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098448-g006: VEGF-induced endothelial and glioma cell migration.A. HMEC-1 and B. C6 glioma cells were cultured in media from cultures of carbon ion-irradiated glioma cells supplemented with VEGF165 (50 ng/ml). C. Quantification of migrating cells. Data represent the mean ± standard error of the mean from at least three independent experiments. D. Expression of phosphorylated FAK (Y861) in cells after addition of VEGF165, as determined by western blotting.
Mentions: To examine the functional significance of altered VEGF level in the culture medium of irradiated tumor cells, conditioned media were supplemented with recombinant VEGF165 (50 ng/ml) and the effect on cell migration was evaluated by wound-healing assay. The migration of HMEC-1 and C6 glioma cells was increased by 1.31- and 1.58-fold, respectively, in the presence of VEGF165 (Fig. 6C). Moreover, after a 4 h incubation in media from carbon ion-irradiated cell cultures supplemented with VEGF165, both cell types showed increases in levels of phosphorylated FAK (Y861) (Fig. 6D).

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