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Metabolic Adaptations in an Endocrine-Related Breast Cancer Mouse Model Unveil Potential Markers of Tumor Response to Hormonal Therapy

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 treat...

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Autores principales: Araújo, Rita, Fabris, Victoria, Lamb, Caroline A., Lanari, Claudia, Helguero, Luisa A., Gil, Ana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921989/
https://www.ncbi.nlm.nih.gov/pubmed/35299741
http://dx.doi.org/10.3389/fonc.2022.786931
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author Araújo, Rita
Fabris, Victoria
Lamb, Caroline A.
Lanari, Claudia
Helguero, Luisa A.
Gil, Ana M.
author_facet Araújo, Rita
Fabris, Victoria
Lamb, Caroline A.
Lanari, Claudia
Helguero, Luisa A.
Gil, Ana M.
author_sort Araújo, Rita
collection PubMed
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.
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spelling pubmed-89219892022-03-16 Metabolic Adaptations in an Endocrine-Related Breast Cancer Mouse Model Unveil Potential Markers of Tumor Response to Hormonal Therapy Araújo, Rita Fabris, Victoria Lamb, Caroline A. Lanari, Claudia Helguero, Luisa A. Gil, Ana M. Front Oncol Oncology 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. Frontiers Media S.A. 2022-03-01 /pmc/articles/PMC8921989/ /pubmed/35299741 http://dx.doi.org/10.3389/fonc.2022.786931 Text en Copyright © 2022 Araújo, Fabris, Lamb, Lanari, Helguero and Gil https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Araújo, Rita
Fabris, Victoria
Lamb, Caroline A.
Lanari, Claudia
Helguero, Luisa A.
Gil, Ana M.
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
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_short 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
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921989/
https://www.ncbi.nlm.nih.gov/pubmed/35299741
http://dx.doi.org/10.3389/fonc.2022.786931
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