Fig. 1: PSCs support cancer cell growth by the secretion of acetate under acidosis.
a, Schematic of NMR-based metabolomics to identify PSC-derived metabolites. b, Metabolites identified in CAF-0911 CM: yellow, increased; blue, decreased; white, unchanged; acetate, red). c, Acetate levels in the interstitial fluid of human PDAC tumours (n = 13) and normal pancreas (n = 3). d, Relative PDAC cell survival with the indicated treatments (n = 3 in each group, from independent biological replicates). e, Immunoblot of ACLY in HPS cells. Representative image of two independent experiments. f, Acetate levels in shScr and shACLY HPS cell–CM compared to serum-free medium (SFM; n = 3 in each group, from independent biological replicates). g, Relative survival of S2-013 cells treated with CM derived from shScr and shACLY HPS cells in normal and low-pH conditions (n = 3 in each group, from independent biological replicates). h,i, Mean organoid diameters (i) and representative images (h) of PA417 and PA901 organoids cultured alone or in combination with shScr or shACLY HPS cells. Scale bars, 100 µm (PA417), 250 µm (PA901) (n = 3 in each group from independent biological replicates). j, Relative survival of PDAC cells treated with CM derived from shScr and shACLY HPS cells under low pH (pH 7.0) with 5 mM acetate (n = 3 in each group, from independent biological replicates). k–o, Tumour weights (k) and volumes (l), Ki-67 IHC staining images (m), Ki-67 quantification in three different fields from three tumours of each (n), and αSMA and ACLY co-expression by IHC (o) upon necropsy from mice implanted with S2-013 cells alone (n = 9) or co-implanted with shScr (n = 7) and shACLY (n = 9) HPS cells. Scale bars, 100 µm (m), 250 µm (o). Images are representative of three tumours of each group. p, Representative images and quantification of αSMA and ACLY colocalization coefficient in normal human pancreas and PDAC tumours. Scale bars, 50 µm. Image are representative of at least two different fields from n = 4 normal human pancreas and n = 23 tumours of each group. Unpaired two-tailed t-test, mean ± s.e.m. (c); two-way analysis of variance (ANOVA) with Šídák’s post-hoc test, mean ± s.e.m. (d); two-way ANOVA with Tukey’s post-hoc test, mean ± s.e.m. (g,j); one-way ANOVA with Bonferroni’s post-hoc test; mean ± s.e.m. (f,i,k,l,n).
