Biological Behavior Of SDF-1 On MM Cells Proliferation,Migration And Adhesion And Corresponding Signaling Pathways

Multiple myeloma(MM) is a neoplasia of plasma cells that are mainly found in the bone marrow(BM) in close association with stromal cells,except at the final stage of disease,when they proliferate in the extramedullary area.At present it hasn't been interpreted that why MM cells mainly invade BM selectively.Rescently Chemokines have been deserving more and more attention for their important role played in tumor metastasis.SDF-1 is a member of β chemokine family, produced by bone marrow stromal cells,can induce B progenitor cells proliferation and modulate B cells maturation.SDF-1 binding to its receptor CXCR4 plays an important role in many kinds of malignant blood cells retention in BM and lymph nodes.So researches targeted at SDF-1/CXCR4 provide a new way for identying the machanism of MM and corresponding therapies.In our research we investigated the biological behavior of SDF-1/CXCR4 on proliferation, migration , adhesion of MM cells and the importance of PI3K in the processes with cytobiology and molecular biology methods.Objective To investigate the biological behavior of SDF-1 on MM cells proliferation, migration and adhesion,and the important role of PI3k played in the processes. Methods We used transwell to assay the effect of SDF-1 on MM cells transmigrion. Activation of PI3K in MM cells treated with SDF-1 was assessed by immunoblotting. Expression of adhesion molecules on MM cells was analysed by flow cytometry and trsnscriptionion of IL-6 and VEGF mRNA were performed by RT-PCR. Immunofluorescence was used to examine the influence of SDF-1 on CD29 and CD44 distribution. Results SDF-1 can stimulate phosphorylation of P85 subunit of PI3K in MM cells and induce MM cells migration, which were both inhibited by G protein inhibitor PTX and PI3K inhibitor wortmannin.Flow cytometry analysis showed that 8226, XG-1 and XG-7respectively overexpressed CD29 and CD44.SDF-1 can not upregulate adhesion molecules expression, but can trigger establishment of a polarized morphology of MM cells and redistribution of CD29 and CD44.SDF-1 upregulated MM cells adhesion to endothelial cells.The blocking antibody of SDF-1 can inhibited MM cells adhesion to endothelial cells and bone marrow stromal cells.After coculture of MM cells and bone marrow stromal cells,expression of IL-6 and VEGF mRNA were both increased. Conclusion SDF-1 can not influence MM cells proliferation, but can trigger establishment of a polarized morphology of MM cells and redistribution of CD29 and CD44 molecules via PI3K signaling pathway,and can promote MM cells migration and their adhesion to endothelial cells and bone marrow stromal cells.