Melanomas often accumulate
gangliosides,
sialic acid-containing
glycosphingolipids found in the outer leaflet of plasma membranes, as disialoganglioside GD3 and its derivatives. Here, we have transfected the GD3 synthase gene (ST8Sia I) in a normal melanocyte cell line in order to evaluate changes in the
biological behavior of non-transformed cells. GD3-synthase expressing cells converted GM3 into GD3 and accumulated both GD3 and its acetylated form, 9-O-acetyl-GD3. Melanocytes were rendered more migratory on
laminin-1 surfaces. Cell migration studies using the different transfectants, either treated or not with the
glucosylceramide synthase inhibitor d-1-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (
PPPP), allowed us to show that while GM3 is a negative regulator of melanocyte migration, GD3 increases it. We showed that
gangliosides were shed to the matrix by migrating cells and that GD3 synthase transfected cells shed extracellular vesicles (EVs) enriched in GD3. EVs enriched in GD3 stimulated cell migration of GD3 negative cells, as observed in time lapse microscopy studies. Otherwise, EVs shed by GM3+veGD3-ve cells impaired migration and diminished cell velocity in cells overexpressing GD3. The balance of antimigratory GM3 and promigratory GD3
gangliosides in melanocytes could be altered not only by the overexpression of
enzymes such as ST8Sia I, but also by the horizontal transfer of
ganglioside enriched extracellular vesicles. This study highlights that extracellular vesicles transfer
biological information also through their membrane components, which include a variety of
glycosphingolipids remodeled in disease states such as
cancer.