Modulation of growth factor signaling by gangliosides: positive or negative?

Increasing evidence has implicated gangliosides, sialic acid-containing cell surface glycosphingolipids, in the biological and clinical behavior of many types of human tumors. Gangliosides are overexpressed and actively shed by tumor cells, can bind to normal cells in the tumor microenvironment, and have a number of biological properties that could conceivably alter tumor-host interactions to influence the survival of the malignant cells that carry these molecules. One major area of investigation is the modulation of cell signaling by gangliosides. Published studies have demonstrated modulation of growth factor signaling through the epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), Trk family, and insulin receptors. Studies conducted over the past 10 y have demonstrated either inhibition or enhancement of signaling by gangliosides, depending on cell type, ganglioside species, and experimental conditions. Of particular concern are conflicting studies that demonstrate opposite effects of gangliosides on the same growth factor receptor. This chapter discusses a methodological approach to addressing this apparent conflict.