Induction of differentiation of WEHI-3B D+ leukemic cells transfected with
differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA
M Tomida
Department of Chemotherapy, Saitama Cancer Center Research Institute,
Japan.
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.
Volume 85,
Issue 1,
pp. 217-221,
01/01/1995
Copyright © 1995 by The American Society of Hematology
