g(m2)-ganglioside and Cell-Transformation--Neoplastic

Continuous cell lines obtained from mouse and hamster embryonic tissue and human lung contain a homologous series of acidic glycolipids known as gangliosides. These complex lipids are highly concentrated in plasma cell membranes. The ganglioside pattern becomes greatly simplified when cells are transformed by tumorigenic DNA and RNA viruses. Non-transforming viruses and lytic infection of cells by tumorigenic viruses without neoplastic tranformation do not cause changes in gangliosides. The alterations of ganglioside composition are the result of specific blocks in the biosynthesis of these lipids. The significance of these impairments of membrane glycolipid formation and the nature of the regulatory site(s) involved are considered with regard to the altered social behavior of transformed cells.

Topics: Animals; Cell Line; Cell Membrane; Cell Transformation, Neoplastic; Chromatography, Gas; Chromatography, Thin Layer; Cricetinae; DNA Viruses; Fibroblasts; Fucosyl Galactose alpha-N-Acetylgalactosaminyltransferase; G(M2) Ganglioside; Gangliosides; HeLa Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; N-Acetyllactosamine Synthase; Oncogenic Viruses; Polyomavirus; RNA Viruses; Sialyltransferases; Simian virus 40

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

Topics: Cell Transformation, Neoplastic; G(M2) Ganglioside; Gangliosides; Glycoproteins; Hexosyltransferases; Mutation; Simian virus 40; Surface Properties; Temperature