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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/6290
Ver los metadatos del registro completo
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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 Técnicas2025-09-03T10:08:27Zoai: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:34982025-09-03 10:08:27.877CONICET 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/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
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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score |
13.13397 |