Extended Data Fig. 10: Primary PDAC development induces a systemic response that promotes the formation of a pro-metastatic niche in the liver.
From: Hepatocytes direct the formation of a pro-metastatic niche in the liver
a, Study design for b–g (n = 4 and 8 for CD45.2 mice injected with PBS (group 1) and PDAC cells (group 2), respectively). b, Assessment of chimaerism in parabiotically joined mice. Flow cytometric analysis of peripheral blood gated on CD45.1+ and CD45.2+ cells as a percentage of CD45+ cells. c, Dorsal (top) and ventral (bottom) views of parabiotically joined mice. Dagger, site of laparotomy for orthotopic injection; double dagger, skin suture for parabiotic joining. d, Images and quantification of myeloid cells and fibronectin. Arrows indicate Ly6G+ cells. e, mRNA levels of Saa. f, Concentration of IL-6 in pancreas supernatant and serum. Solid lines indicate data points from individual mice. Dashed lines indicate the lower limit of detection. g, Concentration of circulating SAA. Data representative of one (f, g) or two independent experiments (a–e). h, i, n = 5 for all groups. h, Images of myeloid cells and fibronectin in the lung of control mice, NTB KPC mice, and tumour-bearing KPC mice. i, Quantification of myeloid cells and fibronectin. Data representative of one experiment (h, i). j, Study design for k–m. k, n = 4 and 5 for Il6+/+ mice and n = 5 and 4 for Il6−/− mice injected with PBS and PDAC cells, respectively. For l, n = 5 for all groups. For m, n = 4 for Stat3flox/flox mice and n = 8 and 7 for Stat3flox/flox Alb-cre mice injected with PBS and PDAC cells, respectively. k–m, Quantification of myeloid cells and fibronectin. Data representative of one experiment (j–m). n, Study design for o (n = 4 for all groups of mice). All groups of mice were injected with PDAC–YFP cells on day 10. o, Quantification of PDAC–YFP cells. Data representative of one experiment (n, o). p, Conceptual model of generation of pro-metastatic niche in the liver. Scale bars, 50 μm. Statistical significance calculated using two-sided Mann–Whitney test (d, e, g), two-sided Wilcoxon test (f), and one-way ANOVA with Dunnett’s test (other panels). NS, not significant. Data represented as mean ± s.d., except d, e, g, which are shown as box plots (centre line, median; box limits, upper and lower quartiles; whiskers, max and min values). Data from individual mice are shown in f.
