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

Carbon ion radiation inhibits glioma and endothelial cell migration induced by secreted VEGF.
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碳离子辐射抑制分泌性 VEGF 诱导的胶质瘤和内皮细胞迁移

DOI:
10.1371/journal.pone.0098448
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang H
Zhang H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu Y;Liu Y;Sun C;Gan L;Zhang L;Mao A;Du Y;Zhou R;Zhang H

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本研究评估了碳离子和X射线辐射以及肿瘤微环境对胶质瘤和内皮细胞迁移的影响,这是癌症进展过程中肿瘤发生和血管生成的关键过程。C6胶质瘤和人微血管内皮细胞用来自在一系列剂量下照射的胶质瘤细胞培养物的条件培养基处理,并评价两种细胞类型的迁移、内皮细胞的管形成以及迁移相关蛋白的表达和分泌。暴露于X射线辐射条件培养基诱导细胞迁移和管形成的剂量依赖性增加,伴随着血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP)-2和-9表达的上调。然而,相对于未照射的细胞,用4.0戈伊碳离子剂量照射的细胞条件培养基处理的胶质瘤细胞显示迁移潜力和VEGF分泌显着降低。应用重组VEGF 165刺激胶质瘤和内皮细胞的迁移,这与FAK Tyr 861磷酸化增加有关,表明碳离子辐射抑制细胞迁移可能是通过VEGF激活FAK信号传导。综上所述,这些发现表明,碳离子可能是上级的X射线辐射抑制肿瘤发生和血管生成,通过调节VEGF水平在胶质瘤微环境。
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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