Extended Data Fig. 7: SAA 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, Concentration of circulating SAA in healthy donors (n = 69), patients with locally advanced PDAC (n = 28), and patients with liver metastases (n = 43). Data represented as a box plot (centre line, median; box limits, upper and lower quartiles; whiskers, max and min values). b, Images of SAA (yellow) and pSTAT3 (purple) in the liver of healthy donors and patients with PDAC with liver metastases. Dashed lines and asterisks indicate sinusoids and hepatocytes, respectively. c, Kaplan–Meier survival curve for patients with PDAC with liver metastases who had low (<250 μg ml–1, black, n = 21) or high (>250 μg ml–1, red, n = 22) levels of circulating SAA. d, Concentration of circulating SAA in patients with locally advanced NSCLC (n = 8) and patients with NSCLC with liver metastases (n = 13). Data shown as a box plot (centre line, median; box limits, upper and lower quartiles; whiskers, max and min values). e, Images of SAA (brown) in the liver of CRC patients with liver metastases. Dashed lines and asterisks indicate sinusoids and hepatocytes, respectively. Data representative of one experiment (a–e). f, g, n = 5 and 4 for Saa+/+ mice and n = 4 and 5 for Saa−/− mice orthotopically injected with PBS or CRC cells (MC-38), respectively. f, Quantification of myeloid cells, fibronectin, and COL1. g, Images of fibronectin (left) and COL1 (right). Data representative of one experiment (f, g). h–o, n = 5 for all groups unless indicated otherwise. h, Images of pSTAT3+ cells, myeloid cells, and fibronectin. i, j, Images and quantification of COL1. k, Images of sinusoids (brown, CD31) in the liver. l, mRNA levels of Lcn2, S100a8, S100a9, Ccl6, Cxcl1, Fn1, Col1a1, and Des in the liver. m, mRNA levels of Saa1 and Saa2. n, Images of pancreas and primary tumour stained for CD31 (brown), CK19 (yellow), and Ki-67 (purple). o, Quantification of the weight of pancreas or primary tumour (left), number of Ki-67+ tumour cells (middle), and vascular area (right). For weight, n = 4 for Saa+/+ mice injected with PDAC cells. Data representative of one (i–k, Fn1, Col1a1, and Des in l, n, o) or two independent experiments (h, all other genes in l, m). p, Study design for q–s (n = 8 and 5 for Saa+/+ mice and n = 5 and 7 for Saa−/− mice injected with PBS and PDAC cells, respectively). All groups were injected with PDAC–YFP cells on day 10. q, r, Images of the liver showing metastatic lesions (yellow, CK19) and Ki-67 (purple). Scale bars, 4 mm (q) and 200 μm (r). s, Quantification of lesions (left) and Ki-67+ tumour cells (right). Data representative of one experiment (p–s). Scale bars, 50 μm unless indicated otherwise. Statistical significance calculated using two-sided Mann–Whitey test (a, d), Mantel–Cox test (c), and one-way ANOVA with Dunnett’s test (other panels). NS, not significant. Data represented as mean ± s.d. unless indicated otherwise.
