Integrin α4 is involved in the regulation of glioma-induced motility of bone marrow mesenchymal stem cells

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 alpha 4 in the motility of BMSCs towards glioma. The role of integrin alpha 4 in the migration of BMSCs towards glioma was evaluated using an in vitro migration assay with the application of a specific integrin alpha 4-blocking antibody. The effect of glioma conditioned medium (CM) on the integrin alpha 4 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-kappa B, PI3K, p38 MAPK, MEK and JNK in the above process. In addition, the role of NF-kappa B 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 alpha 4. The stimulation of glioma CM increased integrin alpha 4 expression of BMSCs. Furthermore, the inhibition of NF-kappa B and PI3K decreased the glioma-induced integrin alpha 4 upregulation on BMSCs. Inhibition of NF-kappa B decreased the number of migrating BMSCs towards gliomas. Glioma cells induced the migration of BMSCs by promoting the expression of integrin alpha 4. NF-kappa B and PI3K contributed to the signal transduction of this process. Similar to PI3K, NF-kappa B 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.