Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures

Autores
Bispo, Daniela; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; Gil, Ana M.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The metabolic characteristics of metastatic and non-metastatic breast carcinomas remain poorly studied. In this work, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was used to compare two medroxyprogesterone acetate (MPA)-induced mammary carcinomas lines with different metastatic abilities. Different metabolic signatures distinguished the non-metastatic (59-2-HI) and the metastatic (C7-2-HI) lines, with glucose, amino acid metabolism, nucleotide metabolism and lipid metabolism as the major affected pathways. Non-metastatic tumours appeared to be characterised by: (a) reduced glycolysis and tricarboxylic acid cycle (TCA) activities, possibly resulting in slower NADH biosynthesis and reduced mitochondrial transport chain activity and ATP synthesis; (b) glutamate accumulation possibly related to reduced glutathione activity and reduced mTORC1 activity; and (c) a clear shift to lower phosphoscholine/glycerophosphocholine ratios and sphingomyelin levels. Within each tumour line, metabolic profiles also differed significantly between tumours (i.e., mice). Metastatic tumours exhibited marked inter-tumour changes in polar compounds, some suggesting different glycolytic capacities. Such tumours also showed larger intra-tumour variations in metabolites involved in nucleotide and cholesterol/fatty acid metabolism, in tandem with less changes in TCA and phospholipid metabolism, compared to non-metastatic tumours. This study shows the valuable contribution of untargeted NMR metabolomics to characterise tumour metabolism, thus opening enticing opportunities to find metabolic markers related to metastatic ability in endocrine breast cancer.
Fil: Bispo, Daniela. 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
NMR
ENDOCRINE BREAST CANCER
HORMONE-INDEPENDENT GROWTH
MEDROXYPROGESTERONE ACETATE
METABOLISM
METABOLOMICS
METASTATIC POTENTIAL
MURINE MODELS
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:11336/132524
Acceder
id CONICETDig_4e4c1c1ffa3acc5f894b7869902ae6bf
oai_identifier_str oai:ri.conicet.gov.ar:11336/132524
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signaturesBispo, DanielaFabris, Victoria TeresaLamb, Caroline AnaLanari, Claudia Lee MalvinaHelguero, Luisa AlejandraGil, Ana M.NMRENDOCRINE BREAST CANCERHORMONE-INDEPENDENT GROWTHMEDROXYPROGESTERONE ACETATEMETABOLISMMETABOLOMICSMETASTATIC POTENTIALMURINE MODELShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The metabolic characteristics of metastatic and non-metastatic breast carcinomas remain poorly studied. In this work, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was used to compare two medroxyprogesterone acetate (MPA)-induced mammary carcinomas lines with different metastatic abilities. Different metabolic signatures distinguished the non-metastatic (59-2-HI) and the metastatic (C7-2-HI) lines, with glucose, amino acid metabolism, nucleotide metabolism and lipid metabolism as the major affected pathways. Non-metastatic tumours appeared to be characterised by: (a) reduced glycolysis and tricarboxylic acid cycle (TCA) activities, possibly resulting in slower NADH biosynthesis and reduced mitochondrial transport chain activity and ATP synthesis; (b) glutamate accumulation possibly related to reduced glutathione activity and reduced mTORC1 activity; and (c) a clear shift to lower phosphoscholine/glycerophosphocholine ratios and sphingomyelin levels. Within each tumour line, metabolic profiles also differed significantly between tumours (i.e., mice). Metastatic tumours exhibited marked inter-tumour changes in polar compounds, some suggesting different glycolytic capacities. Such tumours also showed larger intra-tumour variations in metabolites involved in nucleotide and cholesterol/fatty acid metabolism, in tandem with less changes in TCA and phospholipid metabolism, compared to non-metastatic tumours. This study shows the valuable contribution of untargeted NMR metabolomics to characterise tumour metabolism, thus opening enticing opportunities to find metabolic markers related to metastatic ability in endocrine breast cancer.Fil: Bispo, Daniela. 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; PortugalMDPI AG2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/132524Bispo, Daniela; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures; MDPI AG; Biomolecules; 10; 9; 2020; 1-192218-273X2218-273XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2218-273X/10/9/1242info:eu-repo/semantics/altIdentifier/doi/10.3390/biom10091242info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:52Zoai:ri.conicet.gov.ar:11336/132524instacron: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 09:56:53.325CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
title Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
spellingShingle Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
Bispo, Daniela
NMR
ENDOCRINE BREAST CANCER
HORMONE-INDEPENDENT GROWTH
MEDROXYPROGESTERONE ACETATE
METABOLISM
METABOLOMICS
METASTATIC POTENTIAL
MURINE MODELS
title_short Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
title_full Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
title_fullStr Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
title_full_unstemmed Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
title_sort Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures
dc.creator.none.fl_str_mv Bispo, Daniela
Fabris, Victoria Teresa
Lamb, Caroline Ana
Lanari, Claudia Lee Malvina
Helguero, Luisa Alejandra
Gil, Ana M.
author Bispo, Daniela
author_facet Bispo, Daniela
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 NMR
ENDOCRINE BREAST CANCER
HORMONE-INDEPENDENT GROWTH
MEDROXYPROGESTERONE ACETATE
METABOLISM
METABOLOMICS
METASTATIC POTENTIAL
MURINE MODELS
topic NMR
ENDOCRINE BREAST CANCER
HORMONE-INDEPENDENT GROWTH
MEDROXYPROGESTERONE ACETATE
METABOLISM
METABOLOMICS
METASTATIC POTENTIAL
MURINE MODELS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The metabolic characteristics of metastatic and non-metastatic breast carcinomas remain poorly studied. In this work, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was used to compare two medroxyprogesterone acetate (MPA)-induced mammary carcinomas lines with different metastatic abilities. Different metabolic signatures distinguished the non-metastatic (59-2-HI) and the metastatic (C7-2-HI) lines, with glucose, amino acid metabolism, nucleotide metabolism and lipid metabolism as the major affected pathways. Non-metastatic tumours appeared to be characterised by: (a) reduced glycolysis and tricarboxylic acid cycle (TCA) activities, possibly resulting in slower NADH biosynthesis and reduced mitochondrial transport chain activity and ATP synthesis; (b) glutamate accumulation possibly related to reduced glutathione activity and reduced mTORC1 activity; and (c) a clear shift to lower phosphoscholine/glycerophosphocholine ratios and sphingomyelin levels. Within each tumour line, metabolic profiles also differed significantly between tumours (i.e., mice). Metastatic tumours exhibited marked inter-tumour changes in polar compounds, some suggesting different glycolytic capacities. Such tumours also showed larger intra-tumour variations in metabolites involved in nucleotide and cholesterol/fatty acid metabolism, in tandem with less changes in TCA and phospholipid metabolism, compared to non-metastatic tumours. This study shows the valuable contribution of untargeted NMR metabolomics to characterise tumour metabolism, thus opening enticing opportunities to find metabolic markers related to metastatic ability in endocrine breast cancer.
Fil: Bispo, Daniela. 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 The metabolic characteristics of metastatic and non-metastatic breast carcinomas remain poorly studied. In this work, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was used to compare two medroxyprogesterone acetate (MPA)-induced mammary carcinomas lines with different metastatic abilities. Different metabolic signatures distinguished the non-metastatic (59-2-HI) and the metastatic (C7-2-HI) lines, with glucose, amino acid metabolism, nucleotide metabolism and lipid metabolism as the major affected pathways. Non-metastatic tumours appeared to be characterised by: (a) reduced glycolysis and tricarboxylic acid cycle (TCA) activities, possibly resulting in slower NADH biosynthesis and reduced mitochondrial transport chain activity and ATP synthesis; (b) glutamate accumulation possibly related to reduced glutathione activity and reduced mTORC1 activity; and (c) a clear shift to lower phosphoscholine/glycerophosphocholine ratios and sphingomyelin levels. Within each tumour line, metabolic profiles also differed significantly between tumours (i.e., mice). Metastatic tumours exhibited marked inter-tumour changes in polar compounds, some suggesting different glycolytic capacities. Such tumours also showed larger intra-tumour variations in metabolites involved in nucleotide and cholesterol/fatty acid metabolism, in tandem with less changes in TCA and phospholipid metabolism, compared to non-metastatic tumours. This study shows the valuable contribution of untargeted NMR metabolomics to characterise tumour metabolism, thus opening enticing opportunities to find metabolic markers related to metastatic ability in endocrine breast cancer.
publishDate 2020
dc.date.none.fl_str_mv 2020
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/11336/132524
Bispo, Daniela; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures; MDPI AG; Biomolecules; 10; 9; 2020; 1-19
2218-273X
2218-273X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/132524
identifier_str_mv Bispo, Daniela; Fabris, Victoria Teresa; Lamb, Caroline Ana; Lanari, Claudia Lee Malvina; Helguero, Luisa Alejandra; et al.; Hormone-independent mouse mammary adenocarcinomas with different metastatic potential exhibit different metabolic signatures; MDPI AG; Biomolecules; 10; 9; 2020; 1-19
2218-273X
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.mdpi.com/2218-273X/10/9/1242
info:eu-repo/semantics/altIdentifier/doi/10.3390/biom10091242
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 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 13.13397

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