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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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Effect of radiation on tumor cell migration as assessed by the Boyden chamber migration assay.Representative images are shown of migrating C6 glioma cells exposed to conditioned medium from cultures of A. unirradiated or heavy ion-irradiated, or B. unirradiated or X-ray-irradiated glioma cells. C. Quantification of the number of migratory glioma cells is expressed as means ± standard error of the mean from three independent experiments, in which treatments were performed in triplicate.*P<0.05, ***P<0.001 vs. controls (0 Gy).
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pone-0098448-g001: Effect of radiation on tumor cell migration as assessed by the Boyden chamber migration assay.Representative images are shown of migrating C6 glioma cells exposed to conditioned medium from cultures of A. unirradiated or heavy ion-irradiated, or B. unirradiated or X-ray-irradiated glioma cells. C. Quantification of the number of migratory glioma cells is expressed as means ± standard error of the mean from three independent experiments, in which treatments were performed in triplicate.*P<0.05, ***P<0.001 vs. controls (0 Gy).

Mentions: Cancer cell migration and invasion into adjacent tissues, and intravasation into blood/lymphatic vessels are key events in malignant tumor progression. To investigate the effect of radiation on these processes, glioma and endothelial cells were treated with conditioned media from glioma cell cultures exposed to varying doses of radiation. Tumor-conditioned media from cultures exposed to carbon ion radiation suppressed migration by 11.8% at 2.0 Gy and 17.4% at 4.0 Gy compared to control cells treated with medium from unirradiated cultures after 24 h of exposure (Fig. 1A). In contrast, cell migration was markedly enhanced when media from X-ray-irradiated cultures was used as a chemoattractant (Fig. 1B).


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)

Effect of radiation on tumor cell migration as assessed by the Boyden chamber migration assay.Representative images are shown of migrating C6 glioma cells exposed to conditioned medium from cultures of A. unirradiated or heavy ion-irradiated, or B. unirradiated or X-ray-irradiated glioma cells. C. Quantification of the number of migratory glioma cells is expressed as means ± standard error of the mean from three independent experiments, in which treatments were performed in triplicate.*P<0.05, ***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-g001: Effect of radiation on tumor cell migration as assessed by the Boyden chamber migration assay.Representative images are shown of migrating C6 glioma cells exposed to conditioned medium from cultures of A. unirradiated or heavy ion-irradiated, or B. unirradiated or X-ray-irradiated glioma cells. C. Quantification of the number of migratory glioma cells is expressed as means ± standard error of the mean from three independent experiments, in which treatments were performed in triplicate.*P<0.05, ***P<0.001 vs. controls (0 Gy).
Mentions: Cancer cell migration and invasion into adjacent tissues, and intravasation into blood/lymphatic vessels are key events in malignant tumor progression. To investigate the effect of radiation on these processes, glioma and endothelial cells were treated with conditioned media from glioma cell cultures exposed to varying doses of radiation. Tumor-conditioned media from cultures exposed to carbon ion radiation suppressed migration by 11.8% at 2.0 Gy and 17.4% at 4.0 Gy compared to control cells treated with medium from unirradiated cultures after 24 h of exposure (Fig. 1A). In contrast, cell migration was markedly enhanced when media from X-ray-irradiated cultures was used as a chemoattractant (Fig. 1B).

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