Fig. 1. Mice with NSCLC display increased BCAA uptake and metabolism.

(A and C–E) Mice were fed ¹³C-BCAA containing diet for seven days. (A) Relative ion counts by LC-MS analysis of fully-labeled, free BCAAs in tumors from PDAC and NSCLC mice and normal tissues from their respective control mice. Data are presented as mean ± SEM. N = 4 control and N = 4 PDAC; N = 4 control and N = 4 NSCLC. (B) Diagram of the leucine catabolic pathway. Red labels indicate metabolites measured by mass spectrometry. Blue circles indicate ¹³C-labeled carbons. KIC = α-ketoisocaproate. (C) Relative ion counts by GC-MS analysis of fully-labeled BCAAs from protein acid hydrolysates of tumors from PDAC and NSCLC mice and normal tissues from their respective control mice. Data are presented as mean ± SEM. N = 4 control and N = 4 PDAC; N = 4 control and N = 4 NSCLC. (D) Relative ion counts by LC-MS analysis of fully-labeled KIC in tumors from PDAC and NSCLC mice and normal tissues from their respective control mice. Data are presented as mean ± SEM. N = 4 control and N = 4 PDAC; N = 4 control and N = 4 NSCLC. (E) Citrate M+2 labeling (%) from [U-¹³C]-leucine by GC-MS analysis in tumors from PDAC and NSCLC mice and normal tissues from their respective control mice. Data are presented as mean ± SEM. N = 4 control and N = 4 PDAC; N = 4 control and N = 4 NSCLC. Two-tailed t test was used for all comparisons between two groups. * P<0.05, ** P<0.01, *** P<0.001