Extended Data Fig. 2: Enhanced de novo ornithine synthesis is a distinct feature of PDA.
From: Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer
a, Doubling times of cell lines in Fig. 1b, c. n = 8 biological replicates. b, Percent labeled 15N-proline in 15N-(amine)Gln-fed cells from Fig. 1b, c. n = 4 biological replicates. c, Percent labeled 15N-argininosuccinate (M+4) in 15N4-Arg-fed cells described in Extended Data Fig. 1f, g. n = 4 biological replicates. d,e, Percent 15N-labeled metabolites in AsPC-1 cells fed for 24 h, either 650 μM 15N-(amine)Gln (d) or 64 μM 15N4-Arg (e) in the presence of 64 μM unlabeled arginine (d) or 650 μM unlabeled glutamine (e). These amino acid concentrations reflect levels found in human plasma. n = 4 biological replicates. f,g, Percent labeled 15N-ornithine and 15N-putrescine in 11 cancer cell lines representing 3 cancer types (PDA; BRCA: breast carcinoma; LUAD, lung adenocarcinoma) with tissue-matched normal cell lines (arrowheads), that were fed 15N-(amine)Gln (f) or 15N4-Arg (g) and maintained for 24 h in plasma glutamine and arginine levels as described in d,e. n = 4 biological replicates. h,i, 15N enrichment in plasma glutamine (h) and percent 15N-labeled glutamine in normal pancreas or PDA tumors (i) derived from tumor-bearing iKrasG12D mice and non-tumor-bearing iKrasWT mice treated with Dox (2g l−1 drinking water) for 3 weeks prior to infusion with 15N-(amine)Gln for 1, 2 or 3 h as described in Fig. 1e–g. n = 4 mice per group. j, 15N enrichment in plasma arginine of iKras mice described in Fig. 1g, that were treated with Dox for 3 weeks prior to infusion with 15N4-Arg for 3 h. n = 4 mice per group. k,l, Percent 15N-labeled arginine (k) and relative abundance of total ornithine and putrescine (l) in normal pancreas or PDA tumors derived from either control or tumor-bearing mice described in Fig. 1g, that were infused with 15N4-Arg for 3 h. n = 4 mice per group. Data represent the mean ± s.d. p-values were obtained by one-way (b,c,f,g) or two-way (h–j) ANOVA, followed by Tukey test, or unpaired two-tailed t-test (k,l). In b,f,g, statistical significance is for each cancer cell line vs. its tissue-matched normal cell line/s. In a–g, data are representative of two independent experiments.
