Control of macrophage cell differentiation in human promyelocytic HL-60 leukemia cells by 1,25-dihydroxyvitamin D/sub 3/ and phorbol-12-myristate-13-acetate
Human promyelocytic leukemia cells (HL-60) were induced to differentiate into macrophage-like cells in a dose (3 x 10/sup -10/ to 10/sup -7/ M) and time (1 to 6 days)-dependent manner by 1,25-dihydroxyvitamin D/sub 3/ and the tumor promoter, phorbol-12-myristate-13-acetate. Differentiation was determined by an increase in the percentage of morphologically mature cells, in lysozyme and nonspecific esterase activities, and in reactivity with the murine OKM1 monoclonal antibody. Two HL-60 cell variants, designated as R-80 and B-II, were also examined. R-80 cells, which are resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate, also exhibited resistance, although to a lesser degree, to induction of cell differentiation by 1,25-dihydroxyvitamin D/sub 3/. Te resistance to the action of the two compounds is presumably not due to similar binding sites for the two inducers, since 1,25-dihydroxyvitamin D/sub 3/ was unable to compete for the phorbol diester binding sites as measured by (/sup 3/H)phorbol-12,13-dibutyrate binding. B-II cells were resistant to induction of cell differentiation by 1,25-dihydroxyvitamin D/sub 3/, phorbol-12-myristate-13-acetate, retinoic acid, and dimethyl sulfoxide. Two-dimensional electrophoretic analysis of HL-60 cell protein patterns indicated that treatment of the HL-60 cells with 1,25-dihydroxyvitamin D/sub 3/, phorbol-12-myristate-13-acetate, retinoic acid, and dimethyl sulfoxide caused the cells to express various monocyte-macrophage and granulocyte marker proteins. These results indicate that 1,25-dihydroxyvitamin D/sub 3/ induces in the HL-60 cells a phenotype that resembles, but is not identical to, that of peripheral monocytes-macrophages. 40 references, 3 figures, 1 table.
- Research Organization:
- Argonne National Lab., IL
- DOE Contract Number:
- W-31-109-ENG-38
- OSTI ID:
- 5944553
- Journal Information:
- Cancer Res.; (United States), Vol. 43
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CHOLECALCIFEROL
BIOLOGICAL EFFECTS
DMSO
MACROPHAGES
CELL DIFFERENTIATION
PHORBOL ESTERS
VITAMIN A
CHEMICAL BONDS
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL DATA
LEUKEMIA
MONOCLONAL ANTIBODIES
PROTEINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL CELLS
ANTIBODIES
CARCINOGENS
CONNECTIVE TISSUE CELLS
DATA
DISEASES
ESTERS
HEMIC DISEASES
INFORMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
NEOPLASMS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHAGOCYTES
SOMATIC CELLS
SULFOXIDES
VITAMIN D
VITAMINS
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques