Vascular endothelial growth factor participates in modulating the C6 glioma-induced migration of rat bone marrow-derived mesenchymal stem cells and upregulates their vascular cell adhesion molecule-1 expression.

Vascular endothelial growth factor participates in modulating the C6 glioma-induced migration of rat bone marrow-derived mesenchymal stem cells and upregulates their vascular cell adhesion molecule-1 expression.
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血管内皮生长因子参与调节C6胶质瘤诱导的大鼠骨髓间充质干细胞迁移并上调其血管细胞粘附分子-1表达

DOI:
10.3892/etm.2012.707
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发表时间:
2012-12
影响因子:
2.7
通讯作者:
Liu Y
Liu Y
中科院分区:
医学4区
文献类型:
--
作者:
Gao Z;Cheng P;Xue Y;Liu Y

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骨髓间充质干细胞(BMSCs)已被证明能够向胶质瘤迁移,但负责这种迁移行为的分子机制仍需要进一步阐明。本研究旨在检测血管内皮生长因子(VEGF)在C6胶质瘤诱导的BMSCs迁移中的作用,探讨VEGF对BMSCs迁移能力和血管细胞粘附分子-1(VCAM-1)表达的影响,以及VCAM-1在VEGF诱导BMSCs迁移中的作用。结果表明,C6胶质瘤细胞可显著促进BMSCs的迁移,VEGF中和抗体可部分阻断C6胶质瘤细胞的迁移,20 ng/ml重组大鼠VEGF 164可促进BMSCs的迁移。20 ng/ml VEGF 164孵育12 h可上调BMSCs VCAM-1的表达,阻断VCAM-1可降低VEGF 164诱导的BMSCs迁移。磷脂酰肌醇-3-激酶(PI 3 K)抑制剂LY 294002可抑制VEGF诱导的BMSCs迁移和VCAM-1表达。提示VEGF通过上调VCAM-1表达参与介导C6胶质瘤诱导的BMSCs迁移,PI 3 K参与VEGF 164诱导的BMSCs迁移和VCAM-1表达的信号转导。
Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to be able to migrate towards glioma, but the molecular mechanisms responsible for this migratory behavior still require further elucidation. This study aimed to test the role of vascular endothelial growth factor (VEGF) in the C6 glioma-induced migration of BMSCs, evaluate the effect of VEGF on the migratory capacity and vascular cell adhesion molecule-1 (VCAM-1) expression of BMSCs and explore the role of VCAM-1 in the VEGF-induced migration of BMSCs. The results showed that C6 glioma cells significantly increased the migration of BMSCs in vitro, which was partially blocked by a VEGF neutralizing antibody, and 20 ng/ml recombinant rat VEGF164 incubation enhanced the migration of BMSCs. Moreover, 12 h of 20 ng/ml VEGF164 incubation upregulated the VCAM-1 expression of BMSCs and the blocking of VCAM-1 reduced the VEGF164-induced migration of BMSCs. The data also revealed that LY294002, an inhibitor of phosphoinositide-3-kinase (PI3K), decreased the VEGF-induced migration and VCAM-1 expression of BMSCs. These findings indicate that VEGF participates in mediating the C6 glioma-induced migration of BMSCs by upregulating their VCAM-1 expression, and that PI3K is involved in the signal transduction of VEGF164-induced migration and VCAM-1 expression of BMSCs.
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发表时间: 2011-05-18
影响因子: 9.3
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