Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy

Autores
Araújo, Rita; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; Gil, Ana M.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.
Fil: Araújo, Rita. Universidade de Aveiro; Portugal
Fil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Helguero, Luisa Alejandra. Universidade de Aveiro; Portugal
Fil: Gil, Ana M.. Universidade de Aveiro; Portugal
Materia
ENDOCRINE RELATED BREAST CANCER
MURINE MODEL
METABOLOMICS
METABONOMICS
THERAPY RESISTANCE
BIOMARKERS
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:11336/166190
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/166190
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapyAraújo, RitaFabris, Victoria TeresaLamb, Caroline AnaLanari, Claudia Lee MalvinaHelguero, Luisa AlejandraGil, Ana M.ENDOCRINE RELATED BREAST CANCERMURINE MODELMETABOLOMICSMETABONOMICSTHERAPY RESISTANCEBIOMARKERShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.Fil: Araújo, Rita. Universidade de Aveiro; PortugalFil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Helguero, Luisa Alejandra. Universidade de Aveiro; PortugalFil: Gil, Ana M.. Universidade de Aveiro; PortugalFrontiers Media2022-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/166190Araújo, Rita; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy; Frontiers Media; Frontiers in Oncology; 12; 3-2022; 1-162234-943XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2022.786931/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.786931info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:30Zoai:ri.conicet.gov.ar:11336/166190instacron: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:34982025-09-03 09:45:30.635CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
title Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
spellingShingle Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
Araújo, Rita
ENDOCRINE RELATED BREAST CANCER
MURINE MODEL
METABOLOMICS
METABONOMICS
THERAPY RESISTANCE
BIOMARKERS
title_short Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
title_full Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
title_fullStr Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
title_full_unstemmed Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
title_sort Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy
dc.creator.none.fl_str_mv Araújo, Rita
Fabris, Victoria Teresa
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
Helguero, Luisa Alejandra
Gil, Ana M.
author Araújo, Rita
author_facet Araújo, Rita
Fabris, Victoria Teresa
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
Helguero, Luisa Alejandra
Gil, Ana M.
author_role author
author2 Fabris, Victoria Teresa
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
Helguero, Luisa Alejandra
Gil, Ana M.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ENDOCRINE RELATED BREAST CANCER
MURINE MODEL
METABOLOMICS
METABONOMICS
THERAPY RESISTANCE
BIOMARKERS
topic ENDOCRINE RELATED BREAST CANCER
MURINE MODEL
METABOLOMICS
METABONOMICS
THERAPY RESISTANCE
BIOMARKERS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.
Fil: Araújo, Rita. Universidade de Aveiro; Portugal
Fil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Helguero, Luisa Alejandra. Universidade de Aveiro; Portugal
Fil: Gil, Ana M.. Universidade de Aveiro; Portugal
description Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed.
publishDate 2022
dc.date.none.fl_str_mv 2022-03
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/11336/166190
Araújo, Rita; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy; Frontiers Media; Frontiers in Oncology; 12; 3-2022; 1-16
2234-943X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/166190
identifier_str_mv Araújo, Rita; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy; Frontiers Media; Frontiers in Oncology; 12; 3-2022; 1-16
2234-943X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fonc.2022.786931/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.786931
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
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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 13.13397

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