title: Integrin α4 is involved in the regulation of glioma-induced motility of bone marrow mesenchymal stem cells.
abstract: Bone marrow mesenchymal stem cells (BMSCs) have the ability of migrating towards glioma tissue. However, this migratory behavior remains to be elucidated. The aim of this study was to define the role of integrin α4 in the motility of BMSCs towards glioma. The role of integrin α4 in the migration of BMSCs towards glioma was evaluated using an in vitro migration assay with the application of a specific integrin α4‑blocking antibody. The effect of glioma conditioned medium (CM) on the integrin α4 expression level of BMSCs was assessed by RT-PCR, immunocytochemistry and western blot analysis. BAY11-7082, LY294002, SB203580, PD98059 and SP600125 were used to investigate the role of NF-κB, PI3K, p38 MAPK, MEK and JNK in the above process. In addition, the role of NF-κB in the tropism of BMSCs towards glioma was also evaluated using the in vitro model. The migration of BMSCs towards glioma CM was attenuated by blocking integrin α4. The stimulation of glioma CM increased integrin α4 expression of BMSCs. Furthermore, the inhibition of NF-κB and PI3K decreased the glioma-induced integrin α4 upregulation on BMSCs. Inhibition of NF-κB decreased the number of migrating BMSCs towards gliomas. Glioma cells induced the migration of BMSCs by promoting the expression of integrin α4. NF-κB and PI3K contributed to the signal transduction of this process. Similar to PI3K, NF-κB is associated with the regulation of BMSCs migration toward glioma. Thus, these results may be useful to elucidate the mechanism involved in the glioma-induced migration of BMSCs.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jiang-Chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis* / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D018523:Tropism / Q000235:genetics*
chemical_list: D017077:Culture Media, Conditioned; D016328:NF-kappa B; D039441:Integrin alpha4; D019869:Phosphatidylinositol 3-Kinases