Enhancement of J6-1 human leukemic cell proliferation by membrane-bound M-CSF through a cell-cell contact mechanism II. Role of an M-CSF receptor-like membrane protein.
We have isolated an M-CSF-like membrane-associated growth factor from human leukemic J6-1 cells that can enhance the growth and colony formation of J6-1 cells in vitro. Indirect evidence suggests that this membrane-associated M-CSF-like growth factor may do so by stimulating a corresponding receptor co-expressed on the adjacent J6-1 cells. The objective of this study is to isolate the putative receptor in J6-1 cells by virtue of its ability to bind and thus "block" the growth of J6-1 cells. Based on this approach, we have isolated from the J6-1 cell membrane an inhibitory activity that can inhibit the clonal growth of J6-1 cells. The activity of this inhibitor can be readily neutralized by either anti-M-CSFR MAb or anti-M-CSFR antiserum, suggesting that it is related to M-CSFR, a product of c-fms proto-oncogene. Judging from Sephadex G-200 gel filtration, the molecular weight (MW) of this putative M-CSFR-like inhibitor was estimated to be approx. 150-180 kDa, comparable with that of M-CSFR. The specificity of M-CSFR-like protein to recognize and block membrane-bound M-CSF also was implicated by its ability to upregulate the steady-state levels of c-fms mRNA in J6-1 cells. Besides its antiproliferative activity in vitro, treatment of J6-1 cells with the putative receptor protein before inoculation effectively blocked the growth and tumor formation in vivo by J6-1 cells in a nude mouse model. These findings suggest that the growth and tumor development by J6-1 leukemic cells may involve a contact-mediated "juxtacrine mechanism".
Wu
K F
KF
Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin.
Rao
Q
Q
Zheng
G G
GG
He
Z H
ZH
Ying
H G
HG
Song
Y H
YH
Chen
B D
BD
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D000090063:Proto-Oncogene Mas; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D008565:Membrane Proteins; D000090063:Proto-Oncogene Mas; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor