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Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells
Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying incr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801303/ https://www.ncbi.nlm.nih.gov/pubmed/29456966 http://dx.doi.org/10.3389/fonc.2018.00013 |
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author | Sant’Anna-Silva, Ana Carolina B. Santos, Gilson C. Campos, Samir P. Costa Oliveira Gomes, André Marco Pérez-Valencia, Juan Alberto Rumjanek, Franklin David |
author_facet | Sant’Anna-Silva, Ana Carolina B. Santos, Gilson C. Campos, Samir P. Costa Oliveira Gomes, André Marco Pérez-Valencia, Juan Alberto Rumjanek, Franklin David |
author_sort | Sant’Anna-Silva, Ana Carolina B. |
collection | PubMed |
description | Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by (1)H NMR (nuclear magnetic resonance) spectroscopy. Living, intact cells were also examined by the non-invasive method of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations in the intact cell lines showed that ZsG and LN1 cells displayed high heterogeneity in the energy metabolism, indicating that the cells would oscillate between glycolysis and oxidative metabolism depending on the microenvironment’s composition. However, LN2 cells appeared to have more contributions to the oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional experiments of energy metabolism, mitochondrial physiology, and proliferation assays revealed that all lineages exhibited similar energy features, although resorting to different bioenergetics strategies to face metabolic demands. These differentiated functions may also promote metastasis. We propose that lipid metabolism is related to the increased invasiveness as a result of the accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty acids (CH(2))(n) in parallel with the metastatic potential progression, thus suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways. |
format | Online Article Text |
id | pubmed-5801303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58013032018-02-16 Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells Sant’Anna-Silva, Ana Carolina B. Santos, Gilson C. Campos, Samir P. Costa Oliveira Gomes, André Marco Pérez-Valencia, Juan Alberto Rumjanek, Franklin David Front Oncol Oncology Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by (1)H NMR (nuclear magnetic resonance) spectroscopy. Living, intact cells were also examined by the non-invasive method of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations in the intact cell lines showed that ZsG and LN1 cells displayed high heterogeneity in the energy metabolism, indicating that the cells would oscillate between glycolysis and oxidative metabolism depending on the microenvironment’s composition. However, LN2 cells appeared to have more contributions to the oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional experiments of energy metabolism, mitochondrial physiology, and proliferation assays revealed that all lineages exhibited similar energy features, although resorting to different bioenergetics strategies to face metabolic demands. These differentiated functions may also promote metastasis. We propose that lipid metabolism is related to the increased invasiveness as a result of the accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty acids (CH(2))(n) in parallel with the metastatic potential progression, thus suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways. Frontiers Media S.A. 2018-02-02 /pmc/articles/PMC5801303/ /pubmed/29456966 http://dx.doi.org/10.3389/fonc.2018.00013 Text en Copyright © 2018 Sant’Anna-Silva, Santos, Campos, Oliveira Gomes, Pérez-Valencia and Rumjanek. http://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 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 Sant’Anna-Silva, Ana Carolina B. Santos, Gilson C. Campos, Samir P. Costa Oliveira Gomes, André Marco Pérez-Valencia, Juan Alberto Rumjanek, Franklin David Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title | Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title_full | Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title_fullStr | Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title_full_unstemmed | Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title_short | Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells |
title_sort | metabolic profile of oral squamous carcinoma cell lines relies on a higher demand of lipid metabolism in metastatic cells |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801303/ https://www.ncbi.nlm.nih.gov/pubmed/29456966 http://dx.doi.org/10.3389/fonc.2018.00013 |
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