Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors

Autores
Croci Russo, Diego Omar; Cerliani, Juan Pablo; D'alotto Moreno, Tomas; Mendez Huergo, Santiago Patricio; Mascanfroni, Ivan Darío; Dergan Dylon, Leonardo Sebastian; Toscano, Marta Alicia; Caramelo, Julio Javier; García Vallejo, Juan Jose; Ouyang, Jing; Mesri, Enrique A.; Junttila, Melissa R.; Bais, Carlos; Shipp, Margaret A.; Salatino, Mariana; Rabinovich, Gabriel Adrián
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment.
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Caramelo, Julio Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: García Vallejo, Juan Jose. VU University Medical Center; Países Bajos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Mesri, Enrique A.. University Of Miami; Estados Unidos
Fil: Junttila, Melissa R.. Genentech Inc.; Estados Unidos
Fil: Bais, Carlos. Genentech Inc.; Estados Unidos
Fil: Shipp, Margaret A.. Dana Farber Cancer Institute. Department of Medical Oncology; Estados Unidos
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Materia
Cancer
Anti-Angiogenesis
Glycosylation
Vascular Endothelial Growth Factor Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6290
Acceder
id CONICETDig_655ebda7eada99cc4afa7e8f91d43a54
oai_identifier_str oai:ri.conicet.gov.ar:11336/6290
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumorsCroci Russo, Diego OmarCerliani, Juan PabloD'alotto Moreno, TomasMendez Huergo, Santiago PatricioMascanfroni, Ivan DaríoDergan Dylon, Leonardo SebastianToscano, Marta AliciaCaramelo, Julio JavierGarcía Vallejo, Juan JoseOuyang, JingMesri, Enrique A.Junttila, Melissa R.Bais, CarlosShipp, Margaret A.Salatino, MarianaRabinovich, Gabriel AdriánCancerAnti-AngiogenesisGlycosylationVascular Endothelial Growth Factor Receptorhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment.Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Caramelo, Julio Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García Vallejo, Juan Jose. VU University Medical Center; Países BajosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: Mesri, Enrique A.. University Of Miami; Estados UnidosFil: Junttila, Melissa R.. Genentech Inc.; Estados UnidosFil: Bais, Carlos. Genentech Inc.; Estados UnidosFil: Shipp, Margaret A.. Dana Farber Cancer Institute. Department of Medical Oncology; Estados UnidosFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaCell Press2014-02-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6290Croci Russo, Diego Omar; Cerliani, Juan Pablo; D'alotto Moreno, Tomas; Mendez Huergo, Santiago Patricio; Mascanfroni, Ivan Darío; et al.; Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors; Cell Press; Cell; 156; 4; 13-2-2014; 744-7580092-86741097-4172enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2014.01.043info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867414001366info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:37:03Zoai:ri.conicet.gov.ar:11336/6290instacron: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 10:37:03.862CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
title Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
spellingShingle Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
Croci Russo, Diego Omar
Cancer
Anti-Angiogenesis
Glycosylation
Vascular Endothelial Growth Factor Receptor
title_short Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
title_full Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
title_fullStr Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
title_full_unstemmed Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
title_sort Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors
dc.creator.none.fl_str_mv Croci Russo, Diego Omar
Cerliani, Juan Pablo
D'alotto Moreno, Tomas
Mendez Huergo, Santiago Patricio
Mascanfroni, Ivan Darío
Dergan Dylon, Leonardo Sebastian
Toscano, Marta Alicia
Caramelo, Julio Javier
García Vallejo, Juan Jose
Ouyang, Jing
Mesri, Enrique A.
Junttila, Melissa R.
Bais, Carlos
Shipp, Margaret A.
Salatino, Mariana
Rabinovich, Gabriel Adrián
author Croci Russo, Diego Omar
author_facet Croci Russo, Diego Omar
Cerliani, Juan Pablo
D'alotto Moreno, Tomas
Mendez Huergo, Santiago Patricio
Mascanfroni, Ivan Darío
Dergan Dylon, Leonardo Sebastian
Toscano, Marta Alicia
Caramelo, Julio Javier
García Vallejo, Juan Jose
Ouyang, Jing
Mesri, Enrique A.
Junttila, Melissa R.
Bais, Carlos
Shipp, Margaret A.
Salatino, Mariana
Rabinovich, Gabriel Adrián
author_role author
author2 Cerliani, Juan Pablo
D'alotto Moreno, Tomas
Mendez Huergo, Santiago Patricio
Mascanfroni, Ivan Darío
Dergan Dylon, Leonardo Sebastian
Toscano, Marta Alicia
Caramelo, Julio Javier
García Vallejo, Juan Jose
Ouyang, Jing
Mesri, Enrique A.
Junttila, Melissa R.
Bais, Carlos
Shipp, Margaret A.
Salatino, Mariana
Rabinovich, Gabriel Adrián
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Anti-Angiogenesis
Glycosylation
Vascular Endothelial Growth Factor Receptor
topic Cancer
Anti-Angiogenesis
Glycosylation
Vascular Endothelial Growth Factor Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment.
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mascanfroni, Ivan Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Caramelo, Julio Javier. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: García Vallejo, Juan Jose. VU University Medical Center; Países Bajos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Mesri, Enrique A.. University Of Miami; Estados Unidos
Fil: Junttila, Melissa R.. Genentech Inc.; Estados Unidos
Fil: Bais, Carlos. Genentech Inc.; Estados Unidos
Fil: Shipp, Margaret A.. Dana Farber Cancer Institute. Department of Medical Oncology; Estados Unidos
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
description The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the endothelial cell (EC) surface glycome selectively regulated binding of galectin-1 (Gal1), which upon recognition of complex N-glycans on VEGFR2, activated VEGF-like signaling. Vessels within anti-VEGF-sensitive tumors exhibited high levels of α2-6-linked sialic acid, which prevented Gal1 binding. In contrast, anti-VEGF refractory tumors secreted increased Gal1 and their associated vasculature displayed glycosylation patterns that facilitated Gal1-EC interactions. Interruption of β1-6GlcNAc branching in ECs or silencing of tumor-derived Gal1 converted refractory into anti-VEGF-sensitive tumors, whereas elimination of α2-6-linked sialic acid conferred resistance to anti-VEGF. Disruption of the Gal1-N-glycan axis promoted vascular remodeling, immune cell influx and tumor growth inhibition. Thus, targeting glycosylation-dependent lectin-receptor interactions may increase the efficacy of anti-VEGF treatment.
publishDate 2014
dc.date.none.fl_str_mv 2014-02-13
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/11336/6290
Croci Russo, Diego Omar; Cerliani, Juan Pablo; D'alotto Moreno, Tomas; Mendez Huergo, Santiago Patricio; Mascanfroni, Ivan Darío; et al.; Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors; Cell Press; Cell; 156; 4; 13-2-2014; 744-758
0092-8674
1097-4172
url http://hdl.handle.net/11336/6290
identifier_str_mv Croci Russo, Diego Omar; Cerliani, Juan Pablo; D'alotto Moreno, Tomas; Mendez Huergo, Santiago Patricio; Mascanfroni, Ivan Darío; et al.; Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors; Cell Press; Cell; 156; 4; 13-2-2014; 744-758
0092-8674
1097-4172
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2014.01.043
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867414001366
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
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application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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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