Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro.
Previous studies have demonstrated the tremendous tropism of mesenchymal stem cells (MSCs) for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, the mechanisms underlying the tropism of MSCs for gliomas remain poorly defined. It has been suggested that malignant gliomas secrete a variety of chemokines, including macrophage chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1 alpha (SDF-1 alpha). We isolated and cultured MSCs from rat bone marrow and found that these cells express CCR2 and CXCR4, the respective receptors for MCP-1 and SDF-1 alpha. In vitro analysis revealed that MCP-1 and SDF-1 alpha induce the migration of MSCs. Futhermore, neutralization data suggest that MCP-1 and SDF-1 alpha play a role in the mediation of MSC migration toward gliomas. These results highlight the potential of these cells as a tumor targeting strategy for glioma gene therapy.
Xu
Feng
F
Department of Neurosurgery, Shanghai Neurosurgical Center, Huashan Hospital, Fudan University, Shanghai 200040, PR China. fengxu.dr@gmail.com
Shi
Jinlong
J
Yu
Bin
B
Ni
Wei
W
Wu
Xing
X
Gu
Zhikai
Z
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019718:Receptors, CXCR4