Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells.
Membrane-bound macrophage colony-stimulating factor (m-M-CSF) is the membrane form M-CSF by alternative splicing. J6-1 leukemic cell line spontaneously forms cell clusters, whose growth depends on the auto-juxtacrine mediated by m-M-CSF and its receptor (M-CSFR). In this study, M-CSFR isolated from J6-1 cells and recombinant human M-CSF soluble receptor (rh-M-CSFsR) were used to study their effects on J6-1 cells. Both receptors inhibited cell proliferation. Use of M-CSFR monoclonal antibodies, M-CSFR or rh-M-CSFsR to block either M-CSFR or m-M-CSF on cell surface inhibited the cluster forming process, while both receptors stimulated cells adhering to culture plate. Furthermore, M-CSFR and/or rh-M-CSFsR caused multiple cellular changes including cytoplasmic pH, multinuclear cell ratio, antigen expression and cell diameter. A [Ca(2+)] rise was induced within 90 s by both receptors. Western blot experiments showed that rh-M-CSFsR caused tyrosine phosphorylation on multiple cytoplasmic proteins of 45 kDa and 55-90 kDa, which could be blocked by H7. These observations suggested that m-M-CSF and M-CSFR mediate J6-1 cell intercellular adhesion with bi-directional signal transduction, and Ca(2+), protein tyrosine kinases, PKC and/or other H7 sensitive kinase(s) involve in the counter-directional signal transduction.
Zheng
G
G
National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Tianjin, PR China. zhengggtj@hotmail.com
Rao
Q
Q
Wu
K
K
He
Z
Z
Geng
Y
Y
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor