G(D3) ganglioside-enriched extracellular vesicles stimulate melanocyte migration

Autor(es)

Otake, Andreia Hanada ^[1] ; Saito, Renata de Freitas ^[1] ; Marques Duarte, Ana Paula ^[1] ; Ramos, Alexandre Ferreira ^{[2, 1]} ; Chammas, Roger ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Ctr Translat Res Oncol LIM 24, BR-01246000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS; v. 1864, n. 3, p. 422-432, MAR 2019.
• Citações Web of Science: 1

Resumo

Melanomas often accumulate gangliosides, sialic acid-containing glycosphingolipids found in the outer leaflet of plasma membranes, as disialoganglioside G(D3) and its derivatives. Here, we have transfected the G(D3) synthase gene (ST8Sia I) in a normal melanocyte cell line in order to evaluate changes in the biological behavior of non-transformed cells. G(D3) -synthase expressing cells converted G(M3) into G(D3) and accumulated both G(D3) and its acetylated form, 9-O-acetyl-G(D3). 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-l-propanol (PPPP), allowed us to show that while G(M3) is a negative regulator of melanocyte migration, G(D3) 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 G(D3). EVs enriched in G(D3) stimulated cell migration of G(D3) negative cells, as observed in time lapse microscopy studies. Otherwise, EVs shed by G(M3) (+ve)G(D3)(-ve) cells impaired migration and diminished cell velocity in cells overexpressing G(D3). The balance of antimigratory G(M3) and promigratory G(D3) 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. (AU)

• Processo FAPESP: 14/03742-0 - Projeto temático em medicina translacional: nanopartículas que se ligam a receptores de lipoproteínas no tratamento da aterosclerose, do infarto agudo de miocárdio, do pós-transplante de coração, do câncer e da endometriose
• Beneficiário: Raul Cavalcante Maranhao
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 98/14247-6 - Center for Research on Cell-Based Therapy
• Beneficiário: Marco Antonio Zago
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs