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

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...

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Autores principales:	Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Méndez-Huergo, S.P., Stupirski, J.C., Mazal, D., Osinaga, E., Toscano, M.A., Sundblad, V., Rabinovich, G.A., Salatino, M.
Formato:	JOUR
Materias:	animal cell animal experiment animal model animal tissue article breast biopsy breast cancer breast hyperplasia cancer grading controlled study down regulation female human immune deficiency immunomodulation in vitro study in vivo study lung metastasis lymphocyte function male metastasis inhibition mouse nonhuman pathophysiology priority journal protein expression protein function protein targeting regulatory T lymphocyte spleen tumor growth upregulation wild type Animals Breast Neoplasms Female Galectin 1 Immune Tolerance Lung Neoplasms Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00085472_v73_n3_p1107_DalottoMoreno
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00085472_v73_n3_p1107_DalottoMoreno2023-10-03T14:06:12Z Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease Dalotto-Moreno, T. Croci, D.O. Cerliani, J.P. Martinez-Allo, V.C. Dergan-Dylon, S. Méndez-Huergo, S.P. Stupirski, J.C. Mazal, D. Osinaga, E. Toscano, M.A. Sundblad, V. Rabinovich, G.A. Salatino, M. animal cell animal experiment animal model animal tissue article breast biopsy breast cancer breast hyperplasia cancer grading controlled study down regulation female human immune deficiency immunomodulation in vitro study in vivo study lung metastasis lymphocyte function male metastasis inhibition mouse nonhuman pathophysiology priority journal protein expression protein function protein targeting regulatory T lymphocyte spleen tumor growth upregulation wild type Animals Breast Neoplasms Female Galectin 1 Immune Tolerance Lung Neoplasms Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory 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 thismodel 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 (Treg) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of Treg 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. © 2012 American Association for Cancer Research. Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martinez-Allo, V.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Toscano, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sundblad, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Salatino, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00085472_v73_n3_p1107_DalottoMoreno
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	animal cell animal experiment animal model animal tissue article breast biopsy breast cancer breast hyperplasia cancer grading controlled study down regulation female human immune deficiency immunomodulation in vitro study in vivo study lung metastasis lymphocyte function male metastasis inhibition mouse nonhuman pathophysiology priority journal protein expression protein function protein targeting regulatory T lymphocyte spleen tumor growth upregulation wild type Animals Breast Neoplasms Female Galectin 1 Immune Tolerance Lung Neoplasms Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory
spellingShingle	animal cell animal experiment animal model animal tissue article breast biopsy breast cancer breast hyperplasia cancer grading controlled study down regulation female human immune deficiency immunomodulation in vitro study in vivo study lung metastasis lymphocyte function male metastasis inhibition mouse nonhuman pathophysiology priority journal protein expression protein function protein targeting regulatory T lymphocyte spleen tumor growth upregulation wild type Animals Breast Neoplasms Female Galectin 1 Immune Tolerance Lung Neoplasms Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory Dalotto-Moreno, T. Croci, D.O. Cerliani, J.P. Martinez-Allo, V.C. Dergan-Dylon, S. Méndez-Huergo, S.P. Stupirski, J.C. Mazal, D. Osinaga, E. Toscano, M.A. Sundblad, V. Rabinovich, G.A. Salatino, M. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
topic_facet	animal cell animal experiment animal model animal tissue article breast biopsy breast cancer breast hyperplasia cancer grading controlled study down regulation female human immune deficiency immunomodulation in vitro study in vivo study lung metastasis lymphocyte function male metastasis inhibition mouse nonhuman pathophysiology priority journal protein expression protein function protein targeting regulatory T lymphocyte spleen tumor growth upregulation wild type Animals Breast Neoplasms Female Galectin 1 Immune Tolerance Lung Neoplasms Mice Mice, Inbred BALB C Mice, Inbred C57BL T-Lymphocytes, Regulatory
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 thismodel 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 (Treg) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of Treg 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. © 2012 American Association for Cancer Research.
format	JOUR
author	Dalotto-Moreno, T. Croci, D.O. Cerliani, J.P. Martinez-Allo, V.C. Dergan-Dylon, S. Méndez-Huergo, S.P. Stupirski, J.C. Mazal, D. Osinaga, E. Toscano, M.A. Sundblad, V. Rabinovich, G.A. Salatino, M.
author_facet	Dalotto-Moreno, T. Croci, D.O. Cerliani, J.P. Martinez-Allo, V.C. Dergan-Dylon, S. Méndez-Huergo, S.P. Stupirski, J.C. Mazal, D. Osinaga, E. Toscano, M.A. Sundblad, V. Rabinovich, G.A. Salatino, M.
author_sort	Dalotto-Moreno, T.
title	Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
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
url	http://hdl.handle.net/20.500.12110/paper_00085472_v73_n3_p1107_DalottoMoreno
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Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease

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