title: Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 1:10 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Zhen-jiang
authors.initials: ZJ
authors.lastname: Li
authors.forename: Zi-xing
authors.initials: ZX
authors.lastname: Chen
authors.forename: Jian-nong
authors.initials: JN
authors.lastname: Cen
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Qiao-cheng
authors.initials: QC
authors.lastname: Qiu
mesh_terms: D051926:Basigin / Q000502:physiology; D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019718:Receptors, CXCR4 / Q000502:physiology
chemical_list: C497886:BSG protein, human; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D051926:Basigin