Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis

BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocortic...

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Autores: Zubeldia Plazaola, Arantzazu, Recalde Percaz, Leire, Moragas, Núria, Alcaraz, Mireia, Chen, Xieng, Mancino, Mario, Fernández Nogueira, Patricia, Prats de Puig, Miquel, Guzman, Flavia, Noguera Castells, Aleix, López Plana, Anna, Enreig, Estel, Carbó Carbó, Neus, Almendro Navarro, Vanessa, Gascón, Pere, Bragado, Paloma, Fuster Orellana, Gemma
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132990
Acceso en línea:https://hdl.handle.net/2445/132990
Access Level:acceso abierto
Palabra clave:Càncer de mama
Apoptosi
Glucocorticoides
Estrès (Fisiologia)
Breast cancer
Apoptosis
Glucocorticoids
Stress (Physiology)
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spelling Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosisZubeldia Plazaola, ArantzazuRecalde Percaz, LeireMoragas, NúriaAlcaraz, MireiaChen, XiengMancino, MarioFernández Nogueira, PatriciaPrats de Puig, MiquelGuzman, FlaviaNoguera Castells, AleixLópez Plana, AnnaEnreig, EstelCarbó Carbó, NeusAlmendro Navarro, VanessaGascón, PereBragado, PalomaFuster Orellana, GemmaCàncer de mamaApoptosiGlucocorticoidesEstrès (Fisiologia)Breast cancerApoptosisGlucocorticoidsStress (Physiology)BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells. METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples. RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS. CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.BioMed Central2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132990Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s13058-018-0977-zBreast Cancer Research, 2018, vol. 20, num. 1, p. 65-80https://doi.org/10.1186/s13058-018-0977-zcc-by (c) Zubeldia Plazaola, Arantzazu et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1329902026-05-27T06:46:51Z
dc.title.none.fl_str_mv Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
title Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
spellingShingle Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
Zubeldia Plazaola, Arantzazu
Càncer de mama
Apoptosi
Glucocorticoides
Estrès (Fisiologia)
Breast cancer
Apoptosis
Glucocorticoids
Stress (Physiology)
title_short Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
title_full Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
title_fullStr Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
title_full_unstemmed Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
title_sort Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
dc.creator.none.fl_str_mv Zubeldia Plazaola, Arantzazu
Recalde Percaz, Leire
Moragas, Núria
Alcaraz, Mireia
Chen, Xieng
Mancino, Mario
Fernández Nogueira, Patricia
Prats de Puig, Miquel
Guzman, Flavia
Noguera Castells, Aleix
López Plana, Anna
Enreig, Estel
Carbó Carbó, Neus
Almendro Navarro, Vanessa
Gascón, Pere
Bragado, Paloma
Fuster Orellana, Gemma
author Zubeldia Plazaola, Arantzazu
author_facet Zubeldia Plazaola, Arantzazu
Recalde Percaz, Leire
Moragas, Núria
Alcaraz, Mireia
Chen, Xieng
Mancino, Mario
Fernández Nogueira, Patricia
Prats de Puig, Miquel
Guzman, Flavia
Noguera Castells, Aleix
López Plana, Anna
Enreig, Estel
Carbó Carbó, Neus
Almendro Navarro, Vanessa
Gascón, Pere
Bragado, Paloma
Fuster Orellana, Gemma
author_role author
author2 Recalde Percaz, Leire
Moragas, Núria
Alcaraz, Mireia
Chen, Xieng
Mancino, Mario
Fernández Nogueira, Patricia
Prats de Puig, Miquel
Guzman, Flavia
Noguera Castells, Aleix
López Plana, Anna
Enreig, Estel
Carbó Carbó, Neus
Almendro Navarro, Vanessa
Gascón, Pere
Bragado, Paloma
Fuster Orellana, Gemma
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de mama
Apoptosi
Glucocorticoides
Estrès (Fisiologia)
Breast cancer
Apoptosis
Glucocorticoids
Stress (Physiology)
topic Càncer de mama
Apoptosi
Glucocorticoides
Estrès (Fisiologia)
Breast cancer
Apoptosis
Glucocorticoids
Stress (Physiology)
description BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells. METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples. RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS. CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/132990
url https://hdl.handle.net/2445/132990
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13058-018-0977-z
Breast Cancer Research, 2018, vol. 20, num. 1, p. 65-80
https://doi.org/10.1186/s13058-018-0977-z
dc.rights.none.fl_str_mv cc-by (c) Zubeldia Plazaola, Arantzazu et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Zubeldia Plazaola, Arantzazu et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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