Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells

Autores
Castellaro, Andrés Marcos; Rodriguez, María Celeste; Di Tada, Cecilia E.; Gil, German Alejandro
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced sustained release of pro-inflammatory cytokines from both cell types, activation of NF-κB/STAT3/ERK in the cancer cells and hyperphosphorylation of ERα, which resulted constitutively active. Our simulated tumor microenvironment strongly altered endocrine and inflammatory signaling pathways in breast cancer cells, leading to endocrine resistance in these cells.
Fil: Castellaro, Andrés Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Rodriguez, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Di Tada, Cecilia E.. Fundación Para El Progreso de la Medicina; Argentina
Fil: Gil, German Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Materia
BREAST CANCER
ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
IL-6
MACROPHAGES
NF-ΚB
TAMOXIFEN
TNF-Α
TUMOR MICROENVIRONMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/129163
Acceder
id CONICETDig_1ae00c9215c50f3e72c4916de85e76ce
oai_identifier_str oai:ri.conicet.gov.ar:11336/129163
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cellsCastellaro, Andrés MarcosRodriguez, María CelesteDi Tada, Cecilia E.Gil, German AlejandroBREAST CANCERENDOCRINE RESISTANCEESTROGEN RECEPTORIL-6MACROPHAGESNF-ΚBTAMOXIFENTNF-ΑTUMOR MICROENVIRONMENThttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced sustained release of pro-inflammatory cytokines from both cell types, activation of NF-κB/STAT3/ERK in the cancer cells and hyperphosphorylation of ERα, which resulted constitutively active. Our simulated tumor microenvironment strongly altered endocrine and inflammatory signaling pathways in breast cancer cells, leading to endocrine resistance in these cells.Fil: Castellaro, Andrés Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Rodriguez, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Di Tada, Cecilia E.. Fundación Para El Progreso de la Medicina; ArgentinaFil: Gil, German Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaMDPI AG2019-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129163Castellaro, Andrés Marcos; Rodriguez, María Celeste; Di Tada, Cecilia E.; Gil, German Alejandro; Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells; MDPI AG; Cancers; 11; 2; 2-2019; 1-292072-6694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/cancers11020189info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/11/2/189info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:23:22Zoai:ri.conicet.gov.ar:11336/129163instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:23:23.224CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
title Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
spellingShingle Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
Castellaro, Andrés Marcos
BREAST CANCER
ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
IL-6
MACROPHAGES
NF-ΚB
TAMOXIFEN
TNF-Α
TUMOR MICROENVIRONMENT
title_short Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
title_full Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
title_fullStr Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
title_full_unstemmed Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
title_sort Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells
dc.creator.none.fl_str_mv Castellaro, Andrés Marcos
Rodriguez, María Celeste
Di Tada, Cecilia E.
Gil, German Alejandro
author Castellaro, Andrés Marcos
author_facet Castellaro, Andrés Marcos
Rodriguez, María Celeste
Di Tada, Cecilia E.
Gil, German Alejandro
author_role author
author2 Rodriguez, María Celeste
Di Tada, Cecilia E.
Gil, German Alejandro
author2_role author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
IL-6
MACROPHAGES
NF-ΚB
TAMOXIFEN
TNF-Α
TUMOR MICROENVIRONMENT
topic BREAST CANCER
ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
IL-6
MACROPHAGES
NF-ΚB
TAMOXIFEN
TNF-Α
TUMOR MICROENVIRONMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced sustained release of pro-inflammatory cytokines from both cell types, activation of NF-κB/STAT3/ERK in the cancer cells and hyperphosphorylation of ERα, which resulted constitutively active. Our simulated tumor microenvironment strongly altered endocrine and inflammatory signaling pathways in breast cancer cells, leading to endocrine resistance in these cells.
Fil: Castellaro, Andrés Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Rodriguez, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Di Tada, Cecilia E.. Fundación Para El Progreso de la Medicina; Argentina
Fil: Gil, German Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
description Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models. Proliferation, migration, and colony formation assays were performed to evaluate tamoxifen and ICI 182,780 resistance and confirmed in a mouse-xenograft model. Molecular mechanisms were investigated using cytokine antibody arrays, WB, ELISA, ChIP, siRNA, and qPCR-assays. In our simulated pro-inflammatory tumor microenvironment, tumor-associated macrophages promoted proliferation, migration, invasiveness, and breast tumor growth of ER+ cells, rendering these estrogen-dependent breast cancer cells resistant to estrogen withdrawal and tamoxifen or ICI 182,780 treatment. Crosstalk between breast cancer cells and conditioned macrophages induced sustained release of pro-inflammatory cytokines from both cell types, activation of NF-κB/STAT3/ERK in the cancer cells and hyperphosphorylation of ERα, which resulted constitutively active. Our simulated tumor microenvironment strongly altered endocrine and inflammatory signaling pathways in breast cancer cells, leading to endocrine resistance in these cells.
publishDate 2019
dc.date.none.fl_str_mv 2019-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/129163
Castellaro, Andrés Marcos; Rodriguez, María Celeste; Di Tada, Cecilia E.; Gil, German Alejandro; Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells; MDPI AG; Cancers; 11; 2; 2-2019; 1-29
2072-6694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129163
identifier_str_mv Castellaro, Andrés Marcos; Rodriguez, María Celeste; Di Tada, Cecilia E.; Gil, German Alejandro; Tumor-associated macrophages induce endocrine therapy resistance in ER+ breast cancer cells; MDPI AG; Cancers; 11; 2; 2-2019; 1-29
2072-6694
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers11020189
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/11/2/189
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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