g(m3)-ganglioside and Leukemia--Myeloid--Acute

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

We previously reported that the synthesis of NeuAc(alpha 2-3)Gal(beta 1-4)GlcCer (GM3) ganglioside was preferentially enhanced during the differentiation of HL-60 cells into a monocyte/macrophage lineage induced by 12-O-tetradecanoylphorbol-13-O-acetate (TPA). Since exogenously added GM3 ganglioside was shown to be able to induce the differentiation of HL-60 cells into the monocyte/macrophage lineage in a synthetic medium, the functional role of the GM3 ganglioside increase during the differentiation of HL-60 cells has become the subject of much interest. In the present study, we investigated the activity of CMP-NeuAc:lactosylceramide sialyltransferase, which catalyzes the synthesis of GM3 ganglioside from lactosylceramide, in cells undergoing differentiation induced by two different reagents, TPA and 1 alpha,25-dihydroxy-vitamin D3, which induce the differentiation of HL-60 cells into the monocyte/macrophage lineage through different modes of action. We showed that the activation of CMP-NeuAc:lactosylceramide sialyltransferase and the increase in GM3 ganglioside were not related to the differentiated lineage but to the specific action of TPA, i.e. activation of protein kinase C.

Topics: Calcitriol; Cell Differentiation; Cell Line; Enzyme Activation; G(M3) Ganglioside; Humans; Leukemia, Myeloid, Acute; Phorbol Esters; Phosphorylation; Sialyltransferases; Substrate Specificity; Tetradecanoylphorbol Acetate

GM3 ganglioside, added exogenously to a promyelocytic leukemia cell line (HL-60 cells) in serum-free synthetic medium, induced differentiation into macrophage-like cells. Macrophagic morphology and function of differentiation-induced cells were determined by cell growth behavior, May-Grünwald-Giemsa staining, activities of nonspecific esterase, phagocytosis and nitroblue tetrazolium (NBT) reduction. GM3 ganglioside may play a role in triggering differentiation of HL-60 cells into macrophage-like cells.

Topics: Cell Differentiation; Cell Line; Culture Media; Esterases; G(M3) Ganglioside; Gangliosides; Humans; Leukemia, Myeloid, Acute; Macrophages; Nitroblue Tetrazolium; Phagocytosis

A remarkable increase in monosialo-ganglioside GM3 was observed during the monocytic differentiation of HL-60 cells induced by 12-0-tetradecanoyl-phorbol-13-acetate(TPA). On the other hand, when the cells were cultured with exogenously-added ganglioside GM3 in serum-free conditions, their differentiation along a monocytic lineage was demonstrated with simultaneous complete growth inhibition. Other gangliosides such as ganglioside GM1 showed no effects on cell differentiation, exhibiting instead stimulatory actions on the cell growth. These results indicate that a physiologically-existent, membranous ganglioside GM3, which specifically increases during monocytic cell differentiation, might play a primary role as a trigger in the monocytic cell differentiation.

Topics: Cell Differentiation; Cell Line; Cells, Cultured; Chromatography, Thin Layer; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Granulocytes; Humans; Leukemia, Myeloid, Acute; Monocytes