Figure 1. Efficiently metastasizing melanomas exhibit enhanced lactate uptake in vivo.

Isotope tracing in primary subcutaneous tumors xenografted in NSG mice with efficiently (M405, M481, M487, and UT10) and inefficiently (M715, UM17, UM22, UM43, UM47, M498, M528, M597 and M610) metastasizing melanomas. The number of mice/tumors per treatment is indicated in each panel. a-b, Glucose m+6 as a fraction of the glucose pool (a) and enrichment of other metabolites normalized to m+6 glucose (b) in subcutaneous tumors after [U-¹³C]glucose infusion. c, 3-phosphoglycerate (3PG) m+3 fraction in subcutaneous tumors and lactate m+3 fraction in the plasma of mice infused with [U-¹³C]glucose (20 experiments). d, Tumor lactate concentration (3 experiments). e, Enrichment of metabolites normalized to 3PG m+3 in subcutaneous tumors after [U-¹³C]lactate infusion (23 experiments). f Isotope labelling after [2-²H]lactate infusion (3 experiments). Data represent mean ± s.d. Statistical significance was assessed using t-tests (a and f), paired t-tests (c), log2 t-tests to compare efficient versus inefficient melanomas or Wilcoxon tests to compare metabolites (b and e). Multiple comparisons were adjusted using the Holm-Sidak’s method (b, c, e, and f).