Importance of glycolysis and oxidative phosphorylation in advanced melanoma

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  • Ho, Jonhan
    • Other Affiliation: University of Pittsburgh
  • de Moura, Michelle
    • Other Affiliation: University of Pittsburgh
  • Lin, Yan
    • Other Affiliation: University of Pittsburgh
  • Vincent, Garret
    • Other Affiliation: University of Pittsburgh
  • Thorne, Stephen
    • Other Affiliation: University of Pittsburgh
  • Duncan, Lyn M
    • Other Affiliation: Massachusetts General Hospital
  • Hui-Min, Lin
    • Other Affiliation: University of Pittsburgh
  • Kirkwood, John M
    • Other Affiliation: University of Pittsburgh
  • Becker, Dorothea
    • Other Affiliation: University of Pittsburgh
  • Van Houten, Bennett
    • Other Affiliation: University of Pittsburgh
  • Moschos, Stergios J
    • Affiliation: School of Medicine, Department of Medicine
    • Other Affiliation: University of Pittsburgh
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.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Jonhan Ho et al.; licensee BioMed Central Ltd.
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Journal title
  • Molecular Cancer
Journal volume
  • 11
Journal issue
  • 1
Page start
  • 76
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1476-4598
Bibliographic citation
  • Molecular Cancer. 2012 Oct 09;11(1):76
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • January 4, 2013

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file details 1476-4598-11-76.pdf 2019-05-07 Public Download
file details 1476-4598-11-76.xml 2019-05-07 Public Download
file details Figure S4. 2019-05-07 Public Download
file details Figure S2. 2019-05-07 Public Download
file details Figure S5. MCT1 and MCT4 expression in the nevus>melanoma TMA. The TMA study was performed as described in the legends to Additional files 3 and 4: Figures S3 and S4. 2019-05-07 Public Download
file details Figure S6. 2019-05-07 Public Download
file details Figure S3. 2019-05-07 Public Download
file details Figure S1. Schematic presentation of LDH1-5 and their involvement in OXPHOS and glycolysis. Red circles indicate LDHA subunits and blue circles indicate LDHB subunits. 2019-05-07 Public Download