Platelet-derived growth factor BB promotes the migration of bone marrow-derived mesenchymal stem cells towards C6 glioma and up-regulates the expression of intracellular adhesion molecule-1.
Recent studies have indicated that bone marrow-derived mesenchymal stem cells (BMSCs) have the capacity of migrating towards gliomas. However, few data are available about the molecular mechanism responsible for this migratory capacity. The aim of our study was to investigate the role of platelet-derived growth factor BB (PDGFBB) in the migration of BMSCs towards C6 glioma and evaluate the effect of PDGFBB on the migrating capacity and intercellular adhesion molecule-1 (ICAM-1) expression of BMSCs. The chemokinetic activity of BMSCs in response to C6 glioma-conditioned medium and recombinant rat PDGFBB was analyzed by in vitro migration assay. The effect of PDGFBB on the expression of ICAM-1 was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. Our data showed that C6 glioma-conditioned medium significantly increased the migration of BMSCs, which could be partially blocked by a PDGFBB neutralizing antibody. Recombinant rat PDGFBB enhanced the migration of BMSCs in a concentration-dependent way from 5 to 50ng/ml. Moreover, RT-PCR and immunofluorescence showed that 12h of 20ng/ml PDGFBB incubation could up-regulate the ICAM-1 expression of BMSCs. Our data also revealed that SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), significantly decreased the PDGFBB-induced migration and ICAM-1 expression of BMSCs. These results demonstrate that PDGFBB contributes to the migration of BMSCs towards C6 glioma and up-regulates the expression of ICAM-1, and that p38MAPK is an important signaling molecule correlating with the signal transduction of PDGFBB-induced migration and ICAM-1 expression of BMSCs.
Cheng
Peng
P
Department of Neurosurgery, The First Affiliated Hospital, China Medical University, Nanjingbei Street, No. 151, Heping District, Shenyang, Liaoning Province 110001, PR China.
Gao
Zhi-Qiang
ZQ
Liu
Yun-Hui
YH
Xue
Yi-Xue
YX
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000077214:Becaplermin; D001932:Brain Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000906:Antibodies; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000077214:Becaplermin; D048051:p38 Mitogen-Activated Protein Kinases