Sdf1/Cxcr4 Signalling Promotes Mobility Of Myeloma Cells By Activation And Redistribution Of Cell Surface Adhesion Molecules

Introduction: The aim of the study was to investigate the effects of SDF-1 alpha on multiple myeloma (MM) cell migration, adhesion and their corresponding signalling pathways.Material and methods: We studied the relationship between expression and distribution of the surface adhesion molecules and the ability of MM cells to migrate or adhere to stromal cells with or without SDF-1 alpha in vitro. The effects of activation of phosphatidylinositol 3-kinase (PI3 kinase) in migration of MM cells was also investigated.Results: Flow cytometry analysis showed that MM cells expressed adhesion molecules such as CD29, CD44, CD49d and CD49e. Our results indicated that the SDF-1/CXCR-4 signalling promotes MM cells to adhere to marrow stromal cells in vitro. The migration of MM cells to stromal cells was enhanced in the presence of SDF-1 alpha in a dose-dependent manner, which was inhibited by either pre-incubation of the MM cells with the G protein inhibitor PTX or the PI3 kinase inhibitor wortmannin. Polarization of adhesion molecules was a marked characteristic observed by confocal laser scanning microscopy (CLSM), which might contribute to the cells' migration and adhesion to stromal cells. Meanwhile, we demonstrated that PI3 kinase played a role in the signalling pathway leading to Gi alpha activation triggered by CXCL12 in MM cells. The effects of SDF-1/CXCR-4 signalling in MM cells' polarization and motility might be mediated by Gia alpha, which was required to activate PI3 kinase.Conclusions: Taken together, it is highlighted that SDF-1/CXCR4 is a critical regulator of MM migration, providing the framework for the inhibitors of this pathway to be used in future clinical trials to abrogate MM trafficking.