Aberrant O-glycosylation modulates aggressiveness in neuroblastoma

Autores
Cuello, Héctor Adrián; Segatori, Valeria Inés; Alberto, Marina; Gulino, Cynthia Antonella; Aschero, María del Rosario; Camarero, Sandra; Galluzzo Mutti, Laura; Madauss, Kevin; Alonso, Daniel Fernando; Lubieniecki, Fabiana; Gabri, Mariano Rolando
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status. Our results show a high expression of Lewis glycan family both in MYCN-amplified cell lines and patient samples. Additionally, we report that MYCN-amplified cells overexpressed Core 2-initiating glycosyltransferase C2GNT1 in association with specific ST3Gals and FUTs, and showed increased binding to E- and Pselectins. Silencing of C2GNT1 expression in NB cells diminished expression of Lewis glycans, decreased the E- and P-selectin binding, and reduced cell adhesion, migration and proliferation in vitro. Treatment of MYCN-non-amplified cells with Trichostatin A (TSA), an histone deacetylase inhibitor, increased the expression of Lewis glycans and the enzymes involved in their biosynthesis. Our results demonstrate that MYCNamplified NB cells overexpress Lewis family glycans, which belong to the Core 2 O-glycans group. Their expression plays a key role in the malignant behaviour of the NB cells and it is modulated by epigenetic mechanisms.
Fil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Alberto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Camarero, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Galluzzo Mutti, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Madauss, Kevin. Glaxosmithkline; Estados Unidos
Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Materia
GLYCOPHENOTYPE
HISTONE ACETYLATION
MYCN
NEUROBLASTOMA
O-GLYCANS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/162656
Acceder
id CONICETDig_43e325e0158c0abff39ef2b51eb1c66b
oai_identifier_str oai:ri.conicet.gov.ar:11336/162656
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Aberrant O-glycosylation modulates aggressiveness in neuroblastomaCuello, Héctor AdriánSegatori, Valeria InésAlberto, MarinaGulino, Cynthia AntonellaAschero, María del RosarioCamarero, SandraGalluzzo Mutti, LauraMadauss, KevinAlonso, Daniel FernandoLubieniecki, FabianaGabri, Mariano RolandoGLYCOPHENOTYPEHISTONE ACETYLATIONMYCNNEUROBLASTOMAO-GLYCANShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status. Our results show a high expression of Lewis glycan family both in MYCN-amplified cell lines and patient samples. Additionally, we report that MYCN-amplified cells overexpressed Core 2-initiating glycosyltransferase C2GNT1 in association with specific ST3Gals and FUTs, and showed increased binding to E- and Pselectins. Silencing of C2GNT1 expression in NB cells diminished expression of Lewis glycans, decreased the E- and P-selectin binding, and reduced cell adhesion, migration and proliferation in vitro. Treatment of MYCN-non-amplified cells with Trichostatin A (TSA), an histone deacetylase inhibitor, increased the expression of Lewis glycans and the enzymes involved in their biosynthesis. Our results demonstrate that MYCNamplified NB cells overexpress Lewis family glycans, which belong to the Core 2 O-glycans group. Their expression plays a key role in the malignant behaviour of the NB cells and it is modulated by epigenetic mechanisms.Fil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alberto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Camarero, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Galluzzo Mutti, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Madauss, Kevin. Glaxosmithkline; Estados UnidosFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaImpact Journals2018-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162656Cuello, Héctor Adrián; Segatori, Valeria Inés; Alberto, Marina; Gulino, Cynthia Antonella; Aschero, María del Rosario; et al.; Aberrant O-glycosylation modulates aggressiveness in neuroblastoma; Impact Journals; Oncotarget; 9; 75; 9-2018; 34176-341881949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/26169/text/info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.26169info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:34:47Zoai:ri.conicet.gov.ar:11336/162656instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:34:48.228CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
title Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
spellingShingle Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
Cuello, Héctor Adrián
GLYCOPHENOTYPE
HISTONE ACETYLATION
MYCN
NEUROBLASTOMA
O-GLYCANS
title_short Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
title_full Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
title_fullStr Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
title_full_unstemmed Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
title_sort Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
dc.creator.none.fl_str_mv Cuello, Héctor Adrián
Segatori, Valeria Inés
Alberto, Marina
Gulino, Cynthia Antonella
Aschero, María del Rosario
Camarero, Sandra
Galluzzo Mutti, Laura
Madauss, Kevin
Alonso, Daniel Fernando
Lubieniecki, Fabiana
Gabri, Mariano Rolando
author Cuello, Héctor Adrián
author_facet Cuello, Héctor Adrián
Segatori, Valeria Inés
Alberto, Marina
Gulino, Cynthia Antonella
Aschero, María del Rosario
Camarero, Sandra
Galluzzo Mutti, Laura
Madauss, Kevin
Alonso, Daniel Fernando
Lubieniecki, Fabiana
Gabri, Mariano Rolando
author_role author
author2 Segatori, Valeria Inés
Alberto, Marina
Gulino, Cynthia Antonella
Aschero, María del Rosario
Camarero, Sandra
Galluzzo Mutti, Laura
Madauss, Kevin
Alonso, Daniel Fernando
Lubieniecki, Fabiana
Gabri, Mariano Rolando
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GLYCOPHENOTYPE
HISTONE ACETYLATION
MYCN
NEUROBLASTOMA
O-GLYCANS
topic GLYCOPHENOTYPE
HISTONE ACETYLATION
MYCN
NEUROBLASTOMA
O-GLYCANS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status. Our results show a high expression of Lewis glycan family both in MYCN-amplified cell lines and patient samples. Additionally, we report that MYCN-amplified cells overexpressed Core 2-initiating glycosyltransferase C2GNT1 in association with specific ST3Gals and FUTs, and showed increased binding to E- and Pselectins. Silencing of C2GNT1 expression in NB cells diminished expression of Lewis glycans, decreased the E- and P-selectin binding, and reduced cell adhesion, migration and proliferation in vitro. Treatment of MYCN-non-amplified cells with Trichostatin A (TSA), an histone deacetylase inhibitor, increased the expression of Lewis glycans and the enzymes involved in their biosynthesis. Our results demonstrate that MYCNamplified NB cells overexpress Lewis family glycans, which belong to the Core 2 O-glycans group. Their expression plays a key role in the malignant behaviour of the NB cells and it is modulated by epigenetic mechanisms.
Fil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Alberto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Camarero, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Galluzzo Mutti, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Madauss, Kevin. Glaxosmithkline; Estados Unidos
Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
description Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status. Our results show a high expression of Lewis glycan family both in MYCN-amplified cell lines and patient samples. Additionally, we report that MYCN-amplified cells overexpressed Core 2-initiating glycosyltransferase C2GNT1 in association with specific ST3Gals and FUTs, and showed increased binding to E- and Pselectins. Silencing of C2GNT1 expression in NB cells diminished expression of Lewis glycans, decreased the E- and P-selectin binding, and reduced cell adhesion, migration and proliferation in vitro. Treatment of MYCN-non-amplified cells with Trichostatin A (TSA), an histone deacetylase inhibitor, increased the expression of Lewis glycans and the enzymes involved in their biosynthesis. Our results demonstrate that MYCNamplified NB cells overexpress Lewis family glycans, which belong to the Core 2 O-glycans group. Their expression plays a key role in the malignant behaviour of the NB cells and it is modulated by epigenetic mechanisms.
publishDate 2018
dc.date.none.fl_str_mv 2018-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/162656
Cuello, Héctor Adrián; Segatori, Valeria Inés; Alberto, Marina; Gulino, Cynthia Antonella; Aschero, María del Rosario; et al.; Aberrant O-glycosylation modulates aggressiveness in neuroblastoma; Impact Journals; Oncotarget; 9; 75; 9-2018; 34176-34188
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162656
identifier_str_mv Cuello, Héctor Adrián; Segatori, Valeria Inés; Alberto, Marina; Gulino, Cynthia Antonella; Aschero, María del Rosario; et al.; Aberrant O-glycosylation modulates aggressiveness in neuroblastoma; Impact Journals; Oncotarget; 9; 75; 9-2018; 34176-34188
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/26169/text/
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.26169
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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