Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease

Autores
D'alotto Moreno, Tomas; Croci Russo, Diego Omar; Cerliani, Juan Pablo; Martínez Allo, Verónica Candela; Dergan Dylon, Leonardo Sebastian; Mendez Huergo, Santiago Patricio; Stupirski, Juan Carlos; Mazal, Daniel; Osinaga, Eduardo; Toscano, Marta Alicia; Sundblad, Victoria; Rabinovich, Gabriel Adrián; Salatino, Mariana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.
Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
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: Martínez Allo, Verónica Candela. 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: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mazal, Daniel. Centro Hospitalario Pereira Rossell. Servicio de Anatomía Patologica,; Uruguay
Fil: Osinaga, Eduardo. Universidad de la Republica; Uruguay
Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sundblad, Victoria. 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
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Breast Cancer
Galectin-1
Metastasis
Regulatory T Cells
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:11336/5354
Acceder
id CONICETDig_1851dd3ffec5861bfe911756f87ed834
oai_identifier_str oai:ri.conicet.gov.ar:11336/5354
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic diseaseD'alotto Moreno, TomasCroci Russo, Diego OmarCerliani, Juan PabloMartínez Allo, Verónica CandelaDergan Dylon, Leonardo SebastianMendez Huergo, Santiago PatricioStupirski, Juan CarlosMazal, DanielOsinaga, EduardoToscano, Marta AliciaSundblad, VictoriaRabinovich, Gabriel AdriánSalatino, MarianaBreast CancerGalectin-1MetastasisRegulatory T Cellshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: 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: Martínez Allo, Verónica Candela. 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: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mazal, Daniel. Centro Hospitalario Pereira Rossell. Servicio de Anatomía Patologica,; UruguayFil: Osinaga, Eduardo. Universidad de la Republica; UruguayFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Sundblad, Victoria. 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; ArgentinaFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaAmerican Association For Cancer Research2013-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5354D'alotto Moreno, Tomas; Croci Russo, Diego Omar; Cerliani, Juan Pablo; Martínez Allo, Verónica Candela; Dergan Dylon, Leonardo Sebastian; et al.; Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease; American Association For Cancer Research; Cancer Research; 73; 3; 1-3-2013; 1107-11170008-54721538-7445enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/73/3/1107.longinfo:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-12-2418info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:43:29Zoai:ri.conicet.gov.ar:11336/5354instacron: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:34982025-10-15 15:43:29.861CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
title Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
spellingShingle Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
D'alotto Moreno, Tomas
Breast Cancer
Galectin-1
Metastasis
Regulatory T Cells
title_short Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
title_full Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
title_fullStr Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
title_full_unstemmed Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
title_sort Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
dc.creator.none.fl_str_mv D'alotto Moreno, Tomas
Croci Russo, Diego Omar
Cerliani, Juan Pablo
Martínez Allo, Verónica Candela
Dergan Dylon, Leonardo Sebastian
Mendez Huergo, Santiago Patricio
Stupirski, Juan Carlos
Mazal, Daniel
Osinaga, Eduardo
Toscano, Marta Alicia
Sundblad, Victoria
Rabinovich, Gabriel Adrián
Salatino, Mariana
author D'alotto Moreno, Tomas
author_facet D'alotto Moreno, Tomas
Croci Russo, Diego Omar
Cerliani, Juan Pablo
Martínez Allo, Verónica Candela
Dergan Dylon, Leonardo Sebastian
Mendez Huergo, Santiago Patricio
Stupirski, Juan Carlos
Mazal, Daniel
Osinaga, Eduardo
Toscano, Marta Alicia
Sundblad, Victoria
Rabinovich, Gabriel Adrián
Salatino, Mariana
author_role author
author2 Croci Russo, Diego Omar
Cerliani, Juan Pablo
Martínez Allo, Verónica Candela
Dergan Dylon, Leonardo Sebastian
Mendez Huergo, Santiago Patricio
Stupirski, Juan Carlos
Mazal, Daniel
Osinaga, Eduardo
Toscano, Marta Alicia
Sundblad, Victoria
Rabinovich, Gabriel Adrián
Salatino, Mariana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Galectin-1
Metastasis
Regulatory T Cells
topic Breast Cancer
Galectin-1
Metastasis
Regulatory T Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.
Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
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: Martínez Allo, Verónica Candela. 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: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Mazal, Daniel. Centro Hospitalario Pereira Rossell. Servicio de Anatomía Patologica,; Uruguay
Fil: Osinaga, Eduardo. Universidad de la Republica; Uruguay
Fil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sundblad, Victoria. 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
Fil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.
publishDate 2013
dc.date.none.fl_str_mv 2013-03-01
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/11336/5354
D'alotto Moreno, Tomas; Croci Russo, Diego Omar; Cerliani, Juan Pablo; Martínez Allo, Verónica Candela; Dergan Dylon, Leonardo Sebastian; et al.; Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease; American Association For Cancer Research; Cancer Research; 73; 3; 1-3-2013; 1107-1117
0008-5472
1538-7445
url http://hdl.handle.net/11336/5354
identifier_str_mv D'alotto Moreno, Tomas; Croci Russo, Diego Omar; Cerliani, Juan Pablo; Martínez Allo, Verónica Candela; Dergan Dylon, Leonardo Sebastian; et al.; Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease; American Association For Cancer Research; Cancer Research; 73; 3; 1-3-2013; 1107-1117
0008-5472
1538-7445
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/73/3/1107.long
info:eu-repo/semantics/altIdentifier/doi/10.1158/0008-5472.CAN-12-2418
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
dc.publisher.none.fl_str_mv American Association For Cancer Research
publisher.none.fl_str_mv American Association For Cancer Research
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 13.22299

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