Bone marrow stromal cells isolated from leukemia patients promotes the invasion capacity of SHI-1 cells in vitro and its underlying mechanism / 肿瘤

ABSTRACT

Objective: To investigate the effects of bone marrow stromal cells (BMSCs) isolated from leukemia patients on the invasion capacity leukemia SHI-1 cells in vitro and the underlying mechanism. Methods: BMSCs were isolated from leukemia patients and their conditional culture medium were collected. The expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) in SHI-1 cells and BMSC were detected by RT-PCR. The BMSC and SHI-1 cells were mixed at 1 10 and inoculated in Matrigel-coated transwells. Then CXC chemokine receptor 4 (CXCR4, final concentration of 2 μg/mL) or functional antibody of EMMPRIN were added. The BMSC cultured medium was used as control on cell invasion test. The alteration of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase 2 (TIMP-2), and CXCR4 mRNA were determined by real-time PCR before and after co-culture of SHI-1 cells and BMSC. The content of stromal cell-derived factor 1 (SDF-1) in serum-free supernatent was measured by ELISA. Results: Both SHI-1 and BMSC expressed EMMPRIN. The invasion capacity of SHI-1 cells increased significantly after co-culture with BMSC, which could be blocked by CXCR4 and functional antibody of EMMPRIN. The cultured medium of BMSC did not increase the invasion capacity of SHI-1 cells. The mRNA expression levels of MMP-2, MMP-9, TIMP-2, and CXCR4 as well as SDF-1 contents in serum-free supernatent increased significantly after the SHI-1 cells were co-cultured with BMSC. Conclusion: When BMSC islated from leukemia patients contacted with leukemia SHI-1 cells, they increases the invasion capacity of SHI-1 cells through multiple molecule pathways on the surface of them on cell invasion test. It may be an important mechanism responsible for the invasion of leukemia cells to the outer space of bone marrow.