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

Abstract

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.