Bioactive sialoglycosphingolipids (gangliosides): differentiation-inducers as well as differentiation-markers in human hematopoietic cells

Glycosphingolipids (GSLs), which are amphipathic molecules composed of both hydrophobic and hydrophilic moieties and synthesized by a group of Golgi enzymes, glycosyltransferases, are located almost exclusively on the outer leaflet of plasma membranes of mammalian cells in general, and recently have become known to show an unexpectedly vast molecular heterogeneity. Furthermore, GSLs have been considered to be involved in cellular interactions and cell growth regulations, changing characteristically their composition and biosynthetic pathway during cell development, differentiation and oncogenic transformation although they constitute only a small portion of the cell surface glycoconjugates. In addition, acidic GSLs, gangliosides, have been recently shown to exhibit special receptor-functions for exogenous, bioactive factors such as bacterial toxins, hormones and biological response modifiers. We and other investigators have found that human and murine hemopoietic malignant cells show ganglioside-patterns characteristic of their cell lineages and differentiation-stages, serving an differentiation-markers for both normal and malignant hemopoietic cells, and further, discovered that particular ganglioside molecules themselves, which specifically increase during differentiation along particular cell lineages induced by a variety of chemical agents, exhibit remarkably potent differentiation-inducing and growth-inhibitory activities on human myelogenous leukemia cells. On the basis of these findings, some important biological functions of GSLs, especially gangliosides, will be discussed in special reference to hemopoietic cell differentiation.