title: Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine downregulates matrix metalloproteinase-9 release on J6-1 leukemic cell.
abstract: Earlier studies indicate that J6-1 human leukemic cells proliferate and propagate via the membrane-bound macrophage colony-stimulating factor (M-CSF)-mediated auto-juxtacrine mechanism. Matrix metalloproteinases (MMPs) can modulate the activity of cell membrane molecules and influence many cellular behaviors. Therefore, we hypothesized that MMP may also be involved in the membrane-bound M-CSF-mediated juxtacrine mechanism. First, we investigated whether blocking of membrane-bound M-CSF by neutralizing antibody to M-CSF or M-CSF receptor and adding of exogenous M-CSF are able to influence MMP-9 release. Next, we determined whether MMP-9 participated in J6-1 cells proliferation and influence the shedding of membrane-bound M-CSF and its receptor. Current studies show that blockade of the interaction between membrane-bound M-CSF and M-CSF receptor by antibody to M-CSF or M-CSF receptor promotes MMP-9 release. Moreover, we demonstrated that because of M-CSF mediated juxtacrine, lack of MMP-9 promotes J6-1 cell proliferation, in which a decrease in the shedding of cell-surface M-CSFR is involved. Hence, we suggest that membrane-bound M-CSF inhibit MMP-9 release and down-regulated MMP-9 contribute to juxtacrine stimulating in leukemic cell growth.
authors.affiliation: Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Rao
authors.forename: Guo-Guang
authors.initials: GG
authors.lastname: Zheng
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Wu
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D016173:Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9