Fig. 3

Metabolic signatures reveal that SAG, 2-AG, and ARA are increased in melanoma. Spearman correlation heatmaps of quantified metabolites in (A) skin and (B) melanoma. Red color indicates positive (> 0), white color indicates zero (0), blue color indicates negative (< 0) correlation, and the color intensity represents variation in the levels across the color scale. C Radar chart illustrating the levels of amino acids, neurotransmitters, and bioactive lipids in melanoma and normal skin, quantified by LC–ESI–MS/MS. Data are shown as fold change of the mean values, melanoma levels shown in red, and skin levels in blue, using skin levels as the baseline (fold change 0). D-Q Representative charts of endogenous levels of bioactive lipids in melanoma and skin. Data are shown as violin plots (N = 14 for each group) and analyzed by two-tailed paired t-test; ***P < 0.001; ****P < 0.0001. Abbreviations: 2-AG, 2-arachidonoylglycerol; 2-OG, 2-oleoylglycerol; 20:4 PE, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine; 5-HT, serotonin; Ach, acetylcholine; Ado, L-adenosine; AEA, anandamide; Ala, L-alanine; ARA, arachidonic acid; Arg, L-arginine; Asn, L-asparagine; Asp, L-aspartic acid; C18-20:4 PC, 1-(1Z-octadecenyl)−2-arachidonoyl-sn-glycero-3-phosphocholine; C18-20:4 PE, 1-(1Z-octadecenyl)−2-arachidonoyl-sn-glycero-3-phosphoethanolamine; Cho, choline; CRT, corticosterone; Cys, L-cysteine; ETA, ethanolamine; GABA, gamma-aminobutyric acid; Glu, L-glutamic acid; Gln, L-glutamine; Gly, L-glycine; GSH, glutathione; His, L-histidine; Hist, histamine; LEA, linoleoyl ethanolamide; Leu, L-leucine; Lys, L-lysine; Met, L-methionine; NE, norepinephrine; OEA, oleoyl ethanolamide; PEA, palmitoyl ethanolamide; PGD2, prostaglandin D2; PGE2, prostaglandin E2; Phe, L-phenylalanine; Pro, L- proline; SAG, 1-stearoyl-2-arachidonoyl-sn-glycerol; SEA, stearoyl ethanolamide; Ser, L-serine; Tau, L-taurine; Trp, L-tryptophan; Tyr, L-tyrosine; Val, L-valine