Enhancement of J6-1 human leukemic cell proliferation by cell-cell contact: role of an M-CSF-like membrane-associated growth factor MAF-J6-1.
Density-dependent cell proliferation and cluster formation are growth phenotypes frequently associated with leukemia cells. The secretion of autocrine growth factor, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 1 (IL-1), has been implicated as one possible mechanism in leukemogenesis. In many cases, however, leukemia cells do not appear to produce autocrine growth stimulators. J6-1 is an established human myeloid leukemia cell line that exhibits both density-dependent and cluster-forming growth characteristics. The effect of direct cell-cell contact on J6-1 cell proliferation was investigated. We have isolated from J6-1 cells a membrane-bound factor (designated as MAF-J6-1) that promoted the colony formation by both J6-1 cells and mouse bone marrow CFU-GM. The growth-promoting activity of MAF-J6-1 can be neutralized by either anti-macrophage-CSF (M-CSF or CSF-1) or anti-MAF-J6-1 monoclonal antibodies (MAb), suggesting that MAF-J6-1 is related to M-CSF. Using an immunoblot analysis with anti-MAF-J6-1 MAb, the MW of this membrane-associated factor was estimated to be 80 kDa. Both antibodies also induced a modest growth inhibition on J6-1 cells in vitro. Similarly, addition of exogenous recombinant human M-CSF augmented the colony formation by J6-1 cells, an effect also neutralized by both antibodies. Using an in situ hybridization technique, J6-1 cells were found to express a high level of c-fms proto-oncogene, which encodes the receptor for the M-CSF. Taken together, our results suggest that the membrane-bound MAF-J6-1 promote J6-1 cell proliferation and cluster formation through a 'juxtacrine' mechanism.
Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin.
K F
KF
Wu
Q
Q
Rao
G G
GG
Zheng
Y Q
YQ
Geng
M
M
Li
J
J
Kong
Y H
YH
Song
H G
HG
Ying
B D
BD
Chen
D002450:Cell Communication; D002455:Cell Division; D015870:Gene Expression; D016236:Genes, fms; D006801:Humans; D017403:In Situ Hybridization; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000302:isolation & purification / Q000494:pharmacology*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D014407:Tumor Cells, Cultured / Q000473:pathology
C000715470:MAS1 protein, human; D008565:Membrane Proteins; D000090063:Proto-Oncogene Mas; D016173:Macrophage Colony-Stimulating Factor