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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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 |
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R-134 |
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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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