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Importance of glycolysis and oxidative phosphorylation in advanced melanoma

Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate...

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Autores principales: Ho, Jonhan, de Moura, Michelle Barbi, Lin, Yan, Vincent, Garret, Thorne, Stephen, Duncan, Lyn M, Hui-Min, Lin, Kirkwood, John M, Becker, Dorothea, Van Houten, Bennett, Moschos, Stergios J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537610/
https://www.ncbi.nlm.nih.gov/pubmed/23043612
http://dx.doi.org/10.1186/1476-4598-11-76
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author Ho, Jonhan
de Moura, Michelle Barbi
Lin, Yan
Vincent, Garret
Thorne, Stephen
Duncan, Lyn M
Hui-Min, Lin
Kirkwood, John M
Becker, Dorothea
Van Houten, Bennett
Moschos, Stergios J
author_facet Ho, Jonhan
de Moura, Michelle Barbi
Lin, Yan
Vincent, Garret
Thorne, Stephen
Duncan, Lyn M
Hui-Min, Lin
Kirkwood, John M
Becker, Dorothea
Van Houten, Bennett
Moschos, Stergios J
author_sort Ho, Jonhan
collection PubMed
description Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS), we subsequently determined using tissue microarray (TMA) analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT) 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.
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spelling pubmed-35376102013-01-10 Importance of glycolysis and oxidative phosphorylation in advanced melanoma Ho, Jonhan de Moura, Michelle Barbi Lin, Yan Vincent, Garret Thorne, Stephen Duncan, Lyn M Hui-Min, Lin Kirkwood, John M Becker, Dorothea Van Houten, Bennett Moschos, Stergios J Mol Cancer Research Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS), we subsequently determined using tissue microarray (TMA) analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT) 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy. BioMed Central 2012-10-09 /pmc/articles/PMC3537610/ /pubmed/23043612 http://dx.doi.org/10.1186/1476-4598-11-76 Text en Copyright ©2012 Ho et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ho, Jonhan
de Moura, Michelle Barbi
Lin, Yan
Vincent, Garret
Thorne, Stephen
Duncan, Lyn M
Hui-Min, Lin
Kirkwood, John M
Becker, Dorothea
Van Houten, Bennett
Moschos, Stergios J
Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title_full Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title_fullStr Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title_full_unstemmed Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title_short Importance of glycolysis and oxidative phosphorylation in advanced melanoma
title_sort importance of glycolysis and oxidative phosphorylation in advanced melanoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537610/
https://www.ncbi.nlm.nih.gov/pubmed/23043612
http://dx.doi.org/10.1186/1476-4598-11-76
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