Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA.

Abstract

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.

• Authors: M Tomida
• Journal: Blood (Blood) Vol. 85 Issue 1 Pg. 217-21 (Jan 01 1995) ISSN: 0006-4971 [Print] United States
• PMID: 7528568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Growth Inhibitors
• Interleukin-6
• Leukemia Inhibitory Factor
• Leukemia Inhibitory Factor Receptor alpha Subunit
• Lif protein, mouse
• Lifr protein, mouse
• Lymphokines
• Macrophage-1 Antigen
• Osm protein, mouse
• Peptides
• Receptors, Cytokine
• Receptors, OSM-LIF
• Oncostatin M
• Granulocyte Colony-Stimulating Factor
• Nitroblue Tetrazolium

Topics

• Animals
• Cell Differentiation
• Cell Division
• DNA, Complementary (genetics)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Growth Inhibitors (metabolism, pharmacology)
• Interleukin-6 (pharmacology)
• Leukemia Inhibitory Factor
• Leukemia Inhibitory Factor Receptor alpha Subunit
• Leukemia, Myelomonocytic, Chronic (metabolism, pathology)
• Lymphokines (metabolism, pharmacology)
• Macrophage-1 Antigen (metabolism)
• Mice
• Nitroblue Tetrazolium (metabolism)
• Oncostatin M
• Peptides (pharmacology)
• Receptors, Cytokine (genetics, physiology)
• Receptors, OSM-LIF
• Transfection
• Tumor Cells, Cultured