Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic Signatures
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 abilitie...
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1242 |
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| author | Daniela Bispo Victoria Fabris Caroline A. Lamb Claudia Lanari Luisa A. Helguero Ana M. Gil |
| author_facet | Daniela Bispo Victoria Fabris Caroline A. Lamb Claudia Lanari Luisa A. Helguero Ana M. Gil |
| author_sort | Daniela Bispo |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T16:46:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:46:40Z |
| publishDate | 2020-08-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2adb44845c98433a8b72b40d860ea0402023-11-20T11:33:30ZengMDPI AGBiomolecules2218-273X2020-08-01109124210.3390/biom10091242Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic SignaturesDaniela Bispo0Victoria Fabris1Caroline A. Lamb2Claudia Lanari3Luisa A. Helguero4Ana M. Gil5Department of Chemistry and CICECO—Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, PortugalIByME—Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, Buenos Aires C1428ADN, ArgentinaIByME—Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, Buenos Aires C1428ADN, ArgentinaIByME—Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, Buenos Aires C1428ADN, ArgentinaiBIMED—Institute of Biomedicine, Department of Medical Sciences, Universidade de Aveiro, Agra do Crasto, 3810-193 Aveiro, PortugalDepartment of Chemistry and CICECO—Aveiro Institute of Materials (CICECO/UA), University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, PortugalThe 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.https://www.mdpi.com/2218-273X/10/9/1242endocrine breast cancermurine modelsmetabolismNMRmetabolomicshormone-independent growth |
| spellingShingle | Daniela Bispo Victoria Fabris Caroline A. Lamb Claudia Lanari Luisa A. Helguero Ana M. Gil Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic Signatures Biomolecules endocrine breast cancer murine models metabolism NMR metabolomics hormone-independent growth |
| title | 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_short | 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 |
| topic | endocrine breast cancer murine models metabolism NMR metabolomics hormone-independent growth |
| url | https://www.mdpi.com/2218-273X/10/9/1242 |
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