g(m1)-ganglioside and Leukemia--Myeloid--Acute

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

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

Changes of glycosphingolipids (GSLs) in the bipotential cell differentiation of human promyelocytic leukemia cell line HL-60 cells were investigated by high-performance thin-layer chromatography (HPTLC), with special reference to morphological and functional changes, such as phagocytosis and nitroblue tetrazolium (NBT) reduction. Nine molecular species of neutral GSLs and 13 or more species of sialo-GSLs, ie, gangliosides, were detected on the HPTLC chromatograms for untreated HL-60 cells. The major components were ceramide dihexoside (CDH), GM3, and sialo-paragloboside (SPG). When HL-60 cells were induced to differentiate into both myeloid mature cells and macrophage-like cells in vitro, no new molecular species of GSLs specific for one of the cell differentiations was induced, but distinctive quantitative changes in the GSL composition were definitely observed between the two cell differentiations. During the myeloid differentiation induced by either dimethylsulfoxide (DMSO) or retinoic acid (RA), CDH, paragloboside (PG), and gangliosides having longer sugar moieties characteristically increased with a concomitant decrease of GSLs with shorter sugar chains, such as ceramide monohexoside (CMH) and GM3, and the GSL composition profile of myeloid differentiation-induced HL-60 cells became more similar to that of normal human granulocytes. However, some marked differences were noted between the induced HL-60 cells and the normal granulocytes, especially in the ganglioside compositions. These differences might reflect either some deficiency in the in vitro myeloid differentiation or some leukemic properties of HL-60 cells. In marked contrast to the change of GSL composition during myeloid differentiation, a remarkable increase of GM3, with a concurrent marked decrease of CDH, was observed in the process of cell differentiation into macrophage-like cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which suggested an increase in the biosynthesis of GM3. These results demonstrate that HL-60 cells express distinct GSL profiles, depending not only on maturation stages but also on differentiation directions.

Topics: Cell Line; Cell Transformation, Neoplastic; Dimethyl Sulfoxide; G(M1) Ganglioside; G(M2) Ganglioside; Globosides; Glycosphingolipids; Humans; Leukemia, Myeloid, Acute; Macrophages; Tretinoin