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Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations

Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that...

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Autores principales: Jayaraman, Anusha, Kumar, Praveen, Marin, Silvia, de Atauri, Pedro, Mateo, Francesca, M. Thomson, Timothy, J. Centelles, Josep, F. Graham, Stewart, Cascante, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821452/
https://www.ncbi.nlm.nih.gov/pubmed/29466368
http://dx.doi.org/10.1371/journal.pone.0192175
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author Jayaraman, Anusha
Kumar, Praveen
Marin, Silvia
de Atauri, Pedro
Mateo, Francesca
M. Thomson, Timothy
J. Centelles, Josep
F. Graham, Stewart
Cascante, Marta
author_facet Jayaraman, Anusha
Kumar, Praveen
Marin, Silvia
de Atauri, Pedro
Mateo, Francesca
M. Thomson, Timothy
J. Centelles, Josep
F. Graham, Stewart
Cascante, Marta
author_sort Jayaraman, Anusha
collection PubMed
description Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia. Untargeted high resolution liquid chromatography-mass spectrometry (LC-MS) based metabolomics revealed significant metabolite differences among the various conditions and a total of 25 significantly altered metabolites were identified including acetyl L-carnitine, NAD+, hypoxanthine, guanine and oleamide, with profile changes unique to each of the experimental conditions. Biochemical pathway analysis revealed the importance of fatty acid oxidation and nucleotide salvage pathways. These results provide a global metabolic preview that could help in selectively targeting the ECs aiding in either cancer cell invasion or metastasis in the heterogeneous tumour microenvironment.
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spelling pubmed-58214522018-03-02 Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations Jayaraman, Anusha Kumar, Praveen Marin, Silvia de Atauri, Pedro Mateo, Francesca M. Thomson, Timothy J. Centelles, Josep F. Graham, Stewart Cascante, Marta PLoS One Research Article Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia. Untargeted high resolution liquid chromatography-mass spectrometry (LC-MS) based metabolomics revealed significant metabolite differences among the various conditions and a total of 25 significantly altered metabolites were identified including acetyl L-carnitine, NAD+, hypoxanthine, guanine and oleamide, with profile changes unique to each of the experimental conditions. Biochemical pathway analysis revealed the importance of fatty acid oxidation and nucleotide salvage pathways. These results provide a global metabolic preview that could help in selectively targeting the ECs aiding in either cancer cell invasion or metastasis in the heterogeneous tumour microenvironment. Public Library of Science 2018-02-21 /pmc/articles/PMC5821452/ /pubmed/29466368 http://dx.doi.org/10.1371/journal.pone.0192175 Text en © 2018 Jayaraman et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jayaraman, Anusha
Kumar, Praveen
Marin, Silvia
de Atauri, Pedro
Mateo, Francesca
M. Thomson, Timothy
J. Centelles, Josep
F. Graham, Stewart
Cascante, Marta
Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title_full Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title_fullStr Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title_full_unstemmed Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title_short Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations
title_sort untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with csc and non-csc prostate cancer cell subpopulations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821452/
https://www.ncbi.nlm.nih.gov/pubmed/29466368
http://dx.doi.org/10.1371/journal.pone.0192175
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