Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA.
Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate proliferation of the interleukin-3 (IL-3)-dependent cell line, DA-1a. To determine whether D-factor can induce the differentiation of leukemia cells other than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor receptor in transfected cells was determined by binding of [125]D-factor and analyzed by Scatchard's method. The transfected cells had high-affinity D-factor receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per cell varied from 67 to 1,500 among several clones. The cells expressing a high level of D-factor receptor were induced to differentiate by D-factor; about 60% of the cells exhibited the ability to reduce nitroblue tetrazolium and expression of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The effect of cytokines, which induce the differentiation of M1 cells, on the transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was identical to that against D-factor in the cells of each clone. Expression of D-factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte colony-stimulating factor (G-CSF). Induction of differentiation of the cells accompanied the suppression of proliferation. Treatment of the cells with D-factor for longer than 5 days resulted in 50% inhibition of growth. These results indicate that the stimulating effect of D-factor on the differentiation of malignant myeloid cells is not unique to M1 cells.
Tomida
M
M
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism / Q000473:pathology*; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000235:genetics* / Q000502:physiology; D053606:Receptors, OSM-LIF; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D016177:Macrophage-1 Antigen; C508352:Osm protein, mouse; D010455:Peptides; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053683:Oncostatin M; D016179:Granulocyte Colony-Stimulating Factor; D009580:Nitroblue Tetrazolium