Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 (CXCR4) and extracellular matrix metalloproteinase inducer (EMMPRIN) had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated.</p><p><b>METHODS</b>A co-culture system between SHI-1 cells and bone marrow stromal cells (BMSCs) is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 110 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP-2), and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 (SDF-1) in serum free supernatant was measured by ELISA.</p><p><b>RESULTS</b>Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the coculture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant.</p><p><b>CONCLUSION</b>The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.</p>