Ganglioside GM3: an acidic membrane component that increases during macrophage-like cell differentiation can induce monocytic differentiation of human myeloid and monocytoid leukemic cell lines HL-60 and U937.

Abstract

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 monocytespecific 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-nduction of these cell lines along a monocytic cell lineage.Glycosphingolipids (GSLs) are ubiquitous membrane components and have been shown to be located almost exclusively at the outer leaflet of plasma membranes (1). Dramatic changes in GSL composition and metabolism have been observed during ontogenesis, differentiation, and oncogenic transformation, suggesting a specific role ofmembrane GSLs in regulation of cell growth and cellular interaction (2). GSLs are classified into three major series-i.e., ganglio-, globoand lacto-series, according to their carbohydrate structures. Human promyelocytic leukemia cell line HL-60 cells (3) have been induced to differentiate into mature granulocytes (4, 5) and macrophage-like cells (6) and consist of stem-like cells that are bipotent with respect to myeloid or macrophage differentiation (7). We recently demonstrated that HL-60 cells expressed distinct GSL profiles for two separate pathways of cell differentiation; (i) the lacto-series acidic sialoGSLs, or lacto-series gangliosides, having longer sugar moieties such as sialosylnorhexaosylceramide, increased with a concomitant decrease in the ganglio-series acidic sialo-GSL, or ganglio-series ganglioside, GM3 during granulocytic differentiation; and (ii) in marked contrast to such changes, ganglio-series ganglioside GM3 markedly increased with a concurrent decrease in lacto-series gangliosides in the process of macrophage-like cell differentiation (8). A characteristic increase in ganglio-sefies ganglioside GM3 was also observed during macrophage-like cell differentiation of other human myeloid and monocytic leukemic cell lines such as K562 (9), KG-1 (10), ML-1 (11), and U937 (12) (unpublished data).GSLs exogenously added to the cell culture medium are incorporated into plasma membranes, resulting in enrichment of a particular molecular species ...

Gangliosides Activate Cultured Rat Brain Microglia

“…GM3 but not GM1 inhibited autophosphorylation of the epidermal growth factor receptor (43). GM3 induced monocytic differentiation of HL-60 cells but other gangliosides did not (44). These differential functions of specific types could be because of differences in sialic acid residues.…”

Expression Cloning of Mouse cDNA of CMP-NeuAc:Lactosylceramide α2,3-Sialyltransferase, an Enzyme That Initiates the Synthesis of Gangliosides

“…Almost all mammalian tis- 2 We propose here to assign the name of ST3Gal V to GM3 synthase. HL60 leukemia cells (37). Recently, Yamamura et al (38) reported that GM3 co-localized with various signaling molecules such as c-Src and a low molecular GTP-binding protein Rho on the cell surface of B16 forming a glycolipid-enriched microdomain.…”

Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells

“…Gangliosides are complex glycosphingolipids (GSLs) with N-acetylneuraminic acids (NeuAc), which are major cytoplasmic membrane constituents in mammalian cells, and play important regulatory roles in cell proliferation and differentiation (Svennerholm, 1980;Nojiri et al, 1986;Hakomori, 1990). Cellular gangliosides act as physiological modulators for growth factor mediated cell proliferation (Li et al, 2000).…”