Melanoma tumors exhibit a variable but distinct metabolic signature

Exp Dermatol. 2018 Feb;27(2):204-207. doi: 10.1111/exd.13465. Epub 2018 Jan 10.

Abstract

The Warburg theory of cancer postulates that an important driver of tumorigenesis is insufficient respiration due to mitochondrial defects, and concomitant enhancement of lactate production due to increased aerobic glycolysis. We analysed 48 melanoma samples by immunohistochemistry and found that 38% of melanomas are characterized by areas of isolated or combined deficiencies of complexes of the oxidative phosphorylation (OXPHOS) system, whereby the incidence of OXPHOS-deficient areas is associated with an increased Breslow index; 62% of melanomas showed high expression of all OXPHOS complexes. Expression of carbonic anhydrase IX was low, indicating that melanomas generally are well-oxygenated. Expression of HIF-1α and MCT4 was high, which might be a consequence of increased lactate dehydrogenase A levels in melanomas. Our data indicate that there are two types of melanomas: one that features a classic Warburg effect, whereas the other one, despite being glycolytic, maintains a high level of OXPHOS complexes.

Keywords: Glycolysis; OXPHOS complexes; Warburg effect; hypoxia.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Carbonic Anhydrase IX / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Melanocytes
  • Melanoma / metabolism*
  • Mitochondria / metabolism
  • Monocarboxylic Acid Transporters / metabolism
  • Muscle Proteins / metabolism
  • Oxidative Phosphorylation
  • Oxygen / chemistry
  • Phenotype
  • Phosphorylation
  • Skin Neoplasms / metabolism*

Substances

  • Antigens, Neoplasm
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • SLC16A4 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Oxygen