Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma

Autores
Croci Russo, Diego Omar; Salatino, Mariana; Rubinstein, Natalia; Cerliani, Juan Pablo; Cavallin, Lucas E.; Leung, Howard J.; Ouyang, Jing; Ilarregui, Juan Martin; Toscano, Marta Alicia; Domaica, Carolina Ines; Croci, María C.; Shipp, Margaret A.; Mesri, Enrique A.; Albini, Adriana; Rabinovich, Gabriel Adrián
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rubinstein, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cavallin, Lucas E.. Miami University; Estados Unidos
Fil: Leung, Howard J.. Miami University; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Ilarregui, Juan Martin. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. 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. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Croci, María C.. Universidad Nacional del Comahue; Argentina
Fil: Shipp, Margaret A.. Dana Farber Cancer Institute; Estados Unidos
Fil: Mesri, Enrique A.. Miami University; Estados Unidos
Fil: Albini, Adriana. Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica; Italia
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 Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Materia
Galectin -1
Angiogenesis
Hypoxia
Kaposi'S Sarcoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12352
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12352
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcomaCroci Russo, Diego OmarSalatino, MarianaRubinstein, NataliaCerliani, Juan PabloCavallin, Lucas E.Leung, Howard J.Ouyang, JingIlarregui, Juan MartinToscano, Marta AliciaDomaica, Carolina InesCroci, María C.Shipp, Margaret A.Mesri, Enrique A.Albini, AdrianaRabinovich, Gabriel AdriánGalectin -1AngiogenesisHypoxiaKaposi'S Sarcomahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rubinstein, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Cavallin, Lucas E.. Miami University; Estados UnidosFil: Leung, Howard J.. Miami University; Estados UnidosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: Ilarregui, Juan Martin. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. 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); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Croci, María C.. Universidad Nacional del Comahue; ArgentinaFil: Shipp, Margaret A.. Dana Farber Cancer Institute; Estados UnidosFil: Mesri, Enrique A.. Miami University; Estados UnidosFil: Albini, Adriana. Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica; ItaliaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaRockefeller Univ Press2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12352Croci Russo, Diego Omar; Salatino, Mariana; Rubinstein, Natalia; Cerliani, Juan Pablo; Cavallin, Lucas E.; et al.; Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma; Rockefeller Univ Press; Journal Of Experimental Medicine; 209; 11; 10-2012; 1-160022-1007enginfo:eu-repo/semantics/altIdentifier/url/http://jem.rupress.org/content/209/11/1985info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20111665info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478924/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:33Zoai:ri.conicet.gov.ar:11336/12352instacron: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 10:01:33.794CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
title Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
spellingShingle Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
Croci Russo, Diego Omar
Galectin -1
Angiogenesis
Hypoxia
Kaposi'S Sarcoma
title_short Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
title_full Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
title_fullStr Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
title_full_unstemmed Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
title_sort Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma
dc.creator.none.fl_str_mv Croci Russo, Diego Omar
Salatino, Mariana
Rubinstein, Natalia
Cerliani, Juan Pablo
Cavallin, Lucas E.
Leung, Howard J.
Ouyang, Jing
Ilarregui, Juan Martin
Toscano, Marta Alicia
Domaica, Carolina Ines
Croci, María C.
Shipp, Margaret A.
Mesri, Enrique A.
Albini, Adriana
Rabinovich, Gabriel Adrián
author Croci Russo, Diego Omar
author_facet Croci Russo, Diego Omar
Salatino, Mariana
Rubinstein, Natalia
Cerliani, Juan Pablo
Cavallin, Lucas E.
Leung, Howard J.
Ouyang, Jing
Ilarregui, Juan Martin
Toscano, Marta Alicia
Domaica, Carolina Ines
Croci, María C.
Shipp, Margaret A.
Mesri, Enrique A.
Albini, Adriana
Rabinovich, Gabriel Adrián
author_role author
author2 Salatino, Mariana
Rubinstein, Natalia
Cerliani, Juan Pablo
Cavallin, Lucas E.
Leung, Howard J.
Ouyang, Jing
Ilarregui, Juan Martin
Toscano, Marta Alicia
Domaica, Carolina Ines
Croci, María C.
Shipp, Margaret A.
Mesri, Enrique A.
Albini, Adriana
Rabinovich, Gabriel Adrián
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Galectin -1
Angiogenesis
Hypoxia
Kaposi'S Sarcoma
topic Galectin -1
Angiogenesis
Hypoxia
Kaposi'S Sarcoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Rubinstein, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Cavallin, Lucas E.. Miami University; Estados Unidos
Fil: Leung, Howard J.. Miami University; Estados Unidos
Fil: Ouyang, Jing. Dana Farber Cancer Institute; Estados Unidos
Fil: Ilarregui, Juan Martin. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. 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. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Domaica, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Croci, María C.. Universidad Nacional del Comahue; Argentina
Fil: Shipp, Margaret A.. Dana Farber Cancer Institute; Estados Unidos
Fil: Mesri, Enrique A.. Miami University; Estados Unidos
Fil: Albini, Adriana. Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica; Italia
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 Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
description Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but also for understanding and managing a variety of solid tumors.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/12352
Croci Russo, Diego Omar; Salatino, Mariana; Rubinstein, Natalia; Cerliani, Juan Pablo; Cavallin, Lucas E.; et al.; Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma; Rockefeller Univ Press; Journal Of Experimental Medicine; 209; 11; 10-2012; 1-16
0022-1007
url http://hdl.handle.net/11336/12352
identifier_str_mv Croci Russo, Diego Omar; Salatino, Mariana; Rubinstein, Natalia; Cerliani, Juan Pablo; Cavallin, Lucas E.; et al.; Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis in Kaposi's sarcoma; Rockefeller Univ Press; Journal Of Experimental Medicine; 209; 11; 10-2012; 1-16
0022-1007
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://jem.rupress.org/content/209/11/1985
info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20111665
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478924/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller Univ Press
publisher.none.fl_str_mv Rockefeller Univ 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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