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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author OTAKE, Andreia Hanada FMUSP-HC
SAITO, Renata de Freitas FMUSP-HC
DUARTE, Ana Paula Marques
RAMOS, Alexandre Ferreira FMUSP-HC
dc.date.issued 2019
dc.identifier.citation BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v.1864, n.3, p.422-432, 2019
dc.identifier.issn 1388-1981
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/33066
dc.description.abstract 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.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [1998/14247-6, 2001/01416-9, 2014/03742-0]
dc.language.iso eng
dc.relation.ispartof Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids
dc.rights restrictedAccess
dc.subject Gangliosides; Migration; Melanocyte; Extracellular vesicles
dc.subject.other growth-factor receptor; n-acetyl-gangliosides; gd3 synthase; malignant properties; platelet-adhesion; molecular-cloning; cell-migration; diabetic mice; gm3; expression
dc.title G(D3) ganglioside-enriched extracellular vesicles stimulate melanocyte migration
dc.type article
dc.rights.holder Copyright ELSEVIER SCIENCE BV
dc.description.group LIM/24
dc.identifier.doi 10.1016/j.bbalip.2018.06.014
dc.identifier.pmid 29908366
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author OTAKE, Andreia Hanada:HC:LIM/24
hcfmusp.author SAITO, Renata de Freitas:HC:ICESP
hcfmusp.author RAMOS, Alexandre Ferreira:HC:LIM/24
hcfmusp.author CHAMMAS, Roger:FM:MDR
hcfmusp.author.external · DUARTE, Ana Paula Marques:Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Ctr Translat Res Oncol LIM 24, BR-01246000 Sao Paulo, SP, Brazil
hcfmusp.origem.id WOS:000471838500020
hcfmusp.origem.id 2-s2.0-85049889743
hcfmusp.publisher.city AMSTERDAM
hcfmusp.publisher.country NETHERLANDS
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dc.description.index MEDLINE
dc.identifier.eissn 1879-2618
hcfmusp.citation.wos 0
hcfmusp.affiliation.country Brasil

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