a‒c The migration capabilities of Panc-1 cells were enhanced by the CM of activated CAFs. CAFs were directly co-cultured (a) or Transwell co-cultured with (b) Schwann cells, or cultured with Schwann cells CM (c), respectively. Direct co-culture (a): CM of CAFs, RSC96, and cell mixture of CAFs and RSC96 were harvested. Transwell co-culture (b): CAFs and RSC96 cells were co-cultured via Transwell chambers for 48 h, and CAFs was washed by PBS three times, then CAFs were cultured with fresh medium for another 48 h, at last, CAFs CM was harvested. Schwann cell CM (c): CAFs was cultured with Schwann cell CM for 48 h and the removal of SC-CM was followed by three rinses with PBS, and then CAFs were cultured with fresh medium for another 48 h, at last, CAFs CM was harvested. After 48 h culture with CAFs CM, Panc-1 cells were harvested for migration assay. d The protein levels of E-cadherin, Vimentin, Fibronectin, and β-catenin in Panc-1 cells treated with CM of CAFs, which were cultured with or without (w/ or w/o) RSC96 CM. Data were representative of n = 3 independent experiments. e Schematic diagram of the in vivo orthotopic injection. A cell mixture of CAFs (w/ or w/o RSC96 CM/IL-1RA treatment) and tumor cells was injected into mice pancreas (n = 5). f, g Bioluminescence photograph (f) and quantification (g) of orthotopic tumors of mice injected with a cell mixture of Panc-1 cells and CAFs. h Schematic diagram of in vivo liver metastatic model. Panc-1 (i, j) or CFPAC-1(k, l) were pretreated with ctrl medium (G1), SC-CM(G2), SC-CM+iMDK(G3), ctrl-CAF-CM(G4), SC-induced CAF-CM(G5), or SC + IL-1RA-induced CAF-CM (G6), and then injected via spleen (n = 5). i–l Representative photograph (i, k) and quantification (j, l) of Panc-1 (i, j) or CFPAC-1 (k, l) liver metastatic tumors. a, c (right), Data were the mean ± s.d. of n = 4 independent experiments. b, c (left), g, j, l Data were the mean ± s.d. of n = 5 independent experiments. a–c, e, h Created with BioRender.com. Statistical analysis: unpaired two-sided t-test (a–c, j, l); two-way ANOVA (g). Source data are provided as a Source Data file.