K562 Cell-derived Exosomes Suppress The Adhesive Function Of Bone Marrow Mesenchymal Stem Cells

Background: Chronic myeloid leukemia(CML) is a neoplastic hematologic disorder of hematopoietic stem cells, resulting in the constitutively active tyrosine kinase BCR/ABL oncoprotein. CML is a kind of relatively rare disease involves the 0.3% morbidity of all cancers and 20% of adult leukemia. CML can divide into three stages: chronic phase, accelerate phase and blastic crisis phase owing to the number of leukemia cells in bone marrow and the severity. CML usually presents in a slow progress, but with the time gone, a disease progress is performed, plenty of CML cells are appeared in blood and visceral organs. Because of the decreasing adhesive function of bone marrow microenvironment, immature hematopoietic cells escape through the medullary blood barrier to out of bone marrow. At present, the only way to cure CML completely is the allogeneic hematopoietic stem cell transplantation. Nevertheless, the frequent failure in transplant treatment mainly lies in the weak homing, adhesive and location function of healthy stem cells, which further validate the existence of adhesive defect in CML microenvironment. Exosomes are 30-120 nm vesicles that released from many cell types and carried proteins and RNAs to participate in cell-to-cell communication and mediate the intercellular signal transduction. Given this, our research aims to elaborate the crucial role of CML exosomes in the adhesive function of microenvironment.Objective: The present study was conducted to investigate the influence of K562 cell-derived exosomes to the adhesive function of bone marrow mesenchymal stem cells(BMSCs), and provide a new idea for CML research.Methods: The major experimental methods were as following: the K562 cell-derived exosomes were isolated, BMSCs were separated and cultured, the attachment ability of BMSCs for human cord blood mononuclear cells was tested and the adhesion molecules CD44 and CXCL-12 of BMSCs were tested by western blot and RT-PCR after the co-culture between exosomes and BMSCs, at last array test results of K562 cell-derived exosomes were analysed and mi R-711 expression was validated by q RT-PCR.Results:(1)Exosomes were isolated successfully from K562 cells and BMSCs were cultured successfully;(2)K562 cell-derived exosomes were able to transfer into BMSCs;(3)The attachment ability of BMSCs for human cord blood mononuclear cells was suppressed obviously;(4)The expression of adhesion molecules CD44 and CXCL-12 were decreased after exosomes co-culturing with BMSCs(P<0.05);(5)Mi R-711 expressed in exosomes was 13.28±1.73 folds than in K562 cells.Conclusion: This study confirmed that CML cells could influence BMSCs with the help of exosomes, suppress the expression of adhesion molecules of BMSCs, thus decrease the adhesion and homing for hematopoietic stem cells. It can be caused by the exosomes deliver high concentration mi R-711 to BMSCs. This study provided a new idea for the mechanism of CML progression.