Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions

The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored w...

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Autores principales:	Spallanzani, Raúl Germán, Dalotto Moreno, Tomás, Raffo Iraolagoitia, Ximena Lucía, Ziblat, Andrea, Domaica, Carolina Inés, Ávila, Damián Ezequiel, Rossi, Lucas Ezequiel, Fuertes, Mercedes Beatriz, Battistone, María Agustina, Rabinovich, Gabriel Adrián, Salatino, Mariana, Zwirner, Norberto Walter
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2013
Materias:	Ciencias Médicas Biología Medroxyprogesterone acetate Myeloidderived suppressor cells NK cells Breast cancer
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/136122
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-136122
record_format	dspace
institution	Universidad Nacional de La Plata
institution_str	I-19
repository_str	R-120
collection	SEDICI (UNLP)
language	Inglés
topic	Ciencias Médicas Biología Medroxyprogesterone acetate Myeloidderived suppressor cells NK cells Breast cancer
spellingShingle	Ciencias Médicas Biología Medroxyprogesterone acetate Myeloidderived suppressor cells NK cells Breast cancer Spallanzani, Raúl Germán Dalotto Moreno, Tomás Raffo Iraolagoitia, Ximena Lucía Ziblat, Andrea Domaica, Carolina Inés Ávila, Damián Ezequiel Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz Battistone, María Agustina Rabinovich, Gabriel Adrián Salatino, Mariana Zwirner, Norberto Walter Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
topic_facet	Ciencias Médicas Biología Medroxyprogesterone acetate Myeloidderived suppressor cells NK cells Breast cancer
description	The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth affects myeloid-derived suppressor cells (MDSCs; CD11b⁺Gr-1⁺, mostly CD11b⁺Ly6G⁺Ly6C<sup>int</sup> and CD11b⁺Ly6G⁻Ly6C<sup>high</sup> cells) and natural killer (NK) cells, potentially restraining tumor immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor and expands MDSCs) to challenge BALB/c mice in the absence or in the presence of MPA. We observed that MPA promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA induced a preferential expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells in spleen and bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these cells with the ability to promote a preferential differentiation of bone marrow cells into CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells that displayed suppressive activity on NK cell degranulation. Sorted CD11b⁺Gr-1⁺ cells from MPA-treated tumor-bearing mice exhibited higher suppressive activity on NK cell degranulation than CD11b⁺Gr-1⁺ cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting through the GR, endows tumor cells with an enhanced capacity to expand CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells that subsequently display a stronger suppression of NK cell-mediated anti-tumor immunity. Our results describe an alternative mechanism by which MPA may affect immunosurveillance and have potential implication in breast cancer incidence.
format	Articulo Articulo
author	Spallanzani, Raúl Germán Dalotto Moreno, Tomás Raffo Iraolagoitia, Ximena Lucía Ziblat, Andrea Domaica, Carolina Inés Ávila, Damián Ezequiel Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz Battistone, María Agustina Rabinovich, Gabriel Adrián Salatino, Mariana Zwirner, Norberto Walter
author_facet	Spallanzani, Raúl Germán Dalotto Moreno, Tomás Raffo Iraolagoitia, Ximena Lucía Ziblat, Andrea Domaica, Carolina Inés Ávila, Damián Ezequiel Rossi, Lucas Ezequiel Fuertes, Mercedes Beatriz Battistone, María Agustina Rabinovich, Gabriel Adrián Salatino, Mariana Zwirner, Norberto Walter
author_sort	Spallanzani, Raúl Germán
title	Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
title_short	Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
title_full	Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
title_fullStr	Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
title_full_unstemmed	Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions
title_sort	expansion of cd11b⁺ly6g⁺ly6c<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains nk cell effector functions
publishDate	2013
url	http://sedici.unlp.edu.ar/handle/10915/136122
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Expansion of CD11b⁺Ly6G⁺Ly6C<sup>int</sup> cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions

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