g(m3)-ganglioside and Leukemia--Myeloid

Using tritiated gangliosides [( 3H]-GM3 and [3H]-GM1), characteristic incorporation of exogenous GM3 to HL-60 cells was demonstrated in association with differentiation induction. [3H]-GM3 was bound 4-5 times more than [3H]-GM1 was. Scatchard analysis revealed high and low affinity patterns of binding to the cells. The concentration of GM3 that caused growth inhibition and cell differentiation corresponded well to that which showed the bi-phasic binding pattern. It was strongly suggested that GM3, which induces monocytic differentiation, was characteristically bound and incorporated to the cells around the concentration which caused growth inhibition and cell differentiation.

Topics: Cell Differentiation; G(M3) Ganglioside; Gangliosides; Humans; Kinetics; Leukemia, Myeloid; Tumor Cells, Cultured

The effects of exogenously added glycosphingolipids on the differentiation of mouse myeloid leukemia cells (M1-T22) have been studied. Eight gangliosides and ten neutral glycosphingolipids were tested in terms of their induction of phagocytic activities on the leukemia cells. N-Acetyl-neuraminosyllactosylceramide (NAc-GM3) was the most effective glycolipid for inducing the activity. By the addition of 25 micrograms/ml of NAc-GM3, about 70 percent of the cells acquired phagocytic activity within 20 h incubation. GM1a showed about half the activity of the GM3. In the case of the neutral glycosphingolipids, lactosylceramide (CDH) and globotriaosylceramide (CTH) showed significant effects on the induction of phagocytic activity. Preincubation of the cells with the NAc-GM3 enhanced the effect of dexamethasone as a differentiation inducer on M1-T22 cells. When a human promyelocytic leukemia cell line, HL-60, was preincubated with the NAc-GM3 ganglioside, induction of the phagocytic activity, together with inhibition of the cell growth by phorbol ester (TPA), were markedly enhanced. From these observations, the NAc-GM3 ganglioside seems to act as a modulator of differentiation of mouse myeloid leukemia cells and also of HL-60 cells.

Topics: Animals; Cell Differentiation; Dexamethasone; G(M3) Ganglioside; Gangliosides; Globosides; Glycolipids; Humans; Lactosylceramides; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mice; Phagocytosis; Tetradecanoylphorbol Acetate; Trihexosylceramides; Tumor Cells, Cultured

When human myeloid and monocytoid leukemic cell lines HL-60 and U937, respectively, were treated with an exogenous sialoglycosphingolipid, ganglioside GM3, in serum-free medium, cell growth was markedly inhibited, and their morphological maturation along a monocytic lineage was observed. In addition to a significant increase in phagocytic and nonspecific esterase activities, marked increase of monocyte-specific surface antigens detectable with monoclonal antibodies such as OKM1 and OKM5 was observed in GM3-fed cells. Other sialoglycosphingolipids with the carbohydrate structure belonging to ganglio-series oligosaccharide, ganglioside GM1 and a brain ganglioside mixture, had no effect on the cell differentiation, showing instead stimulatory actions on the growth of these cell lines. We recently demonstrated that the ganglio-series ganglioside GM3 characteristically increased during macrophage-like cell differentiation of these cell lines. The present results indicate that ganglioside molecular species that specifically increase during monocytic cell differentiation of human myeloid and monocytoid leukemic cell lines may play, in turn, an important role in the differentiation-induction of these cell lines along a monocytic cell lineage.

Topics: Animals; Antibodies, Monoclonal; Cattle; Cell Differentiation; Cell Line; Cell Transformation, Neoplastic; Dogs; Dose-Response Relationship, Drug; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes

Topics: Adult; Cell Differentiation; Cell Membrane; Chromatography, Thin Layer; G(M3) Ganglioside; Gangliosides; Humans; Leukemia, Myeloid; Middle Aged; Neutrophils