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Importance of glycolysis and oxidative phosphorylation in advanced melanoma

Ho, J and de Moura, MB and Lin, Y and Vincent, G and Thorne, S and Duncan, LM and Hui-Min, L and Kirkwood, JM and Becker, D and Van Houten, B and Moschos, SJ (2012) Importance of glycolysis and oxidative phosphorylation in advanced melanoma. Molecular Cancer, 11.

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Abstract

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. © 2012 Ho et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ho, Jjoh19@pitt.eduJOH19
de Moura, MB
Lin, Yyal14@pitt.eduYAL14
Vincent, Ggav10@pitt.eduGAV10
Thorne, Ssht38@pitt.eduSHT38
Duncan, LM
Hui-Min, L
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Becker, D
Van Houten, Bbev15@pitt.eduBEV15
Moschos, SJ
Date: 9 October 2012
Date Type: Publication
Journal or Publication Title: Molecular Cancer
Volume: 11
DOI or Unique Handle: 10.1186/1476-4598-11-76
Schools and Programs: Graduate School of Public Health > Biostatistics
School of Medicine > Medicine
School of Medicine > Pathology
School of Medicine > Pharmacology and Chemical Biology
School of Medicine > Surgery
Refereed: Yes
Date Deposited: 02 Dec 2016 14:55
Last Modified: 27 Feb 2019 09:55
URI: http://d-scholarship.pitt.edu/id/eprint/29816

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