Gao Zhiqiang, Cheng Peng, Xue Yixue, Liu Yunhui
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004;
Exp Ther Med. 2012 Dec;4(6):993-998. doi: 10.3892/etm.2012.707. Epub 2012 Sep 14.
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 VEGF(164) incubation enhanced the migration of BMSCs. Moreover, 12 h of 20 ng/ml VEGF(164) incubation upregulated the VCAM-1 expression of BMSCs and the blocking of VCAM-1 reduced the VEGF(164)-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 VEGF(164)-induced migration and VCAM-1 expression of BMSCs.
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进一步阐明。本研究旨在测试血管内皮生长因子(VEGF)在C6胶质瘤诱导的BMSCs迁移中的作用,评估VEGF对BMSCs迁移能力和血管细胞黏附分子-1(VCAM-1)表达的影响,并探讨VCAM-1在VEGF诱导的BMSCs迁移中的作用。结果表明,C6胶质瘤细胞在体外显著增加了BMSCs的迁移,这一过程被VEGF中和抗体部分阻断,并且20 ng/ml重组大鼠VEGF(164)孵育增强了BMSCs的迁移。此外,20 ng/ml VEGF(164)孵育12小时上调了BMSCs的VCAM-1表达,阻断VCAM-1降低了VEGF(164)诱导的BMSCs迁移。数据还显示,磷酸肌醇-3-激酶(PI3K)抑制剂LY294002降低了VEGF诱导的BMSCs迁移和VCAM-1表达。这些发现表明,VEGF通过上调BMSCs的VCAM-1表达参与介导C6胶质瘤诱导的BMSCs迁移,并且PI3K参与VEGF(164)诱导的BMSCs迁移和VCAM-1表达的信号转导。