Artículo

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" (2013) Cancer Research. 73(3):1107-1117
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Abstract:

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.

Registro:

Documento: Artículo
Título:Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
Autor: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.
Filiación:Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Servicio de Anatomía Patológica, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay, Uruguay
Departamento de Inmunobiología, Facultad de Medicina, Montevideo, Uruguay, Uruguay
Mariana Salatino, Laboratorio de Inmunopatología, IBYME, Vuelta de Obligado 2490, C1428, Buenos Aires, Argentina
Palabras clave: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
Año:2013
Volumen:73
Número:3
Página de inicio:1107
Página de fin:1117
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-12-2418
Título revista:Cancer Research
Título revista abreviado:Cancer Res.
ISSN:00085472
CODEN:CNREA
CAS:Galectin 1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00085472_v73_n3_p1107_DalottoMoreno

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Citas:

---------- APA ----------
Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Méndez-Huergo, S.P., Stupirski, J.C.,..., Salatino, M. (2013) . Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Research, 73(3), 1107-1117.
http://dx.doi.org/10.1158/0008-5472.CAN-12-2418
---------- CHICAGO ----------
Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Méndez-Huergo, S.P., et al. "Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease" . Cancer Research 73, no. 3 (2013) : 1107-1117.
http://dx.doi.org/10.1158/0008-5472.CAN-12-2418
---------- MLA ----------
Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Méndez-Huergo, S.P., et al. "Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease" . Cancer Research, vol. 73, no. 3, 2013, pp. 1107-1117.
http://dx.doi.org/10.1158/0008-5472.CAN-12-2418
---------- VANCOUVER ----------
Dalotto-Moreno, T., Croci, D.O., Cerliani, J.P., Martinez-Allo, V.C., Dergan-Dylon, S., Méndez-Huergo, S.P., et al. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res. 2013;73(3):1107-1117.
http://dx.doi.org/10.1158/0008-5472.CAN-12-2418