Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic Signatures
authors Bispo, D; Fabris, V; Lamb, CA; Lanari, C; Helguero, LA; Gil, AM
nationality International
journal BIOMOLECULES
author keywords endocrine breast cancer; murine models; metabolism; NMR; metabolomics; hormone-independent growth; metastatic potential; medroxyprogesterone acetate
keywords BREAST-CANCER CELLS; MASS-SPECTROMETRY; PHOSPHOLIPID PROFILES; GLUTAMINE-METABOLISM; TUMOR HETEROGENEITY; EXPRESSION; MRS; REVEALS; SAMPLES; PATHWAY
abstract 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.
publisher MDPI
isbn 2218-273X
year published 2020
volume 10
issue 9
digital object identifier (doi) 10.3390/biom10091242
web of science category Biochemistry & Molecular Biology
subject category Biochemistry & Molecular Biology
unique article identifier WOS:000581315300001
  ciceco authors
  impact metrics
journal analysis (jcr 2019):
journal impact factor 4.082
5 year journal impact factor Not Available
category normalized journal impact factor percentile 67.172
dimensions (citation analysis):
altmetrics (social interaction):



 


Sponsors

1suponsers_list_ciceco.jpg