Expression And Significance Of UPA System In Co-culture Model Of Bone Marrow Stromal Cell-leukemia Cells

The urokinase plasminogen activator(uPA)system consists of uPA,its cognate receptor(uPAR)and two specific inhibitors,the plasminogen activator inhibitor 1(PAI-1)and 2(PAI-2).It is closely associated with a variety of human malignancies of local invasion and metastasis,which is an important molecular target for the treatment of tumors.In this study,in order to explore the interaction between uPA system and leukemia bone marrow microenvironment,we used real-time fluorescence quantitative PCR and ELISA to study the expression of uPA,uPAR,PAI-1,MMP-9 and VEGF in direct contact co-culture of leukemia bone marrow stromal cells and leukemia cells HL60.Results showed that the expressions of uPA,uPAR,PAI-1 and VEGF in the co-cultured HBMSCs were significantly higher than that in mono-cultured cells.Meanwhile,MMP-9 was upregulated in co-cultured HL60.The increased expressions of uPA,uPAR and PAI-1 in co-BMSCs can further explain why leukemia cells are closely associated with the uPA system in the growth,development,recurrence in the bone marrow microenvironment and poor prognosis of leukemia.The expression of MMP-9 in HL60 was elevated under co-culture conditions,which may explain the mechanism of bone marrow microenvironment how to contribute to the proliferation of leukemia cells.