Fig. 6: Schwann cells induce a phenotypic switch in CAFs via IL-1α. | Nature Communications

Fig. 6: Schwann cells induce a phenotypic switch in CAFs via IL-1α.

From: Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment

Fig. 6: Schwann cells induce a phenotypic switch in CAFs via IL-1α.The alternative text for this image may have been generated using AI.

a The relative mRNA levels of iCAF and myCAF markers in CAF-2 cultured with RSC96 CM and control. b The protein level of α-SMA in CAF-2 cultured with 0, 20, or 100 μg/ml RSC96 CM. c The fold change of IL-6 in CAF-2 cultured with RSC96 CM for 0, 1, 6, or 24 h was evaluated by ELISA. d Representative images and quantification of IF with anti-α-SMA in CAF-2 cultured with RSC96 CM and control. Scale bar, 100 µm. Images are representative of three biologically independent experiments with CAF-2 cells with similar results. e QuSAGE scores of control and SC-CM associated signature in perineural tier 1–4 and other regions in the neuro-stroma niche. The signatures were defined by the bulk RNA-seq of CAFs with SC-CM treatment. f Schematic diagram of ex vivo assay. g The relative mRNA levels of iCAF and myCAF markers in PDAC tissue cultured with RSC96 CM and control. h, i Representative images (h) and quantification (i) of IF with anti-α-SMA and IL-6 in PDAC tissue cultured with RSC96 CM and control. Scale bar, 20 µm. j Representative images and quantification of IL-1α in PDAC tissues. Scale bar, 20 µm. h, j Images are representative of five PDAC samples with similar results. k The relative mRNA levels of iCAF and myCAF markers in CAF-2 treated with IL-1α or RSC96 CM. l The relative mRNA levels of iCAF and myCAF markers in CAF-2 cultured by RSC96 CM pretreated with neutralization antibodies against IL-1α or IgG control. m Schematic diagram of how Schwann cells shape tumor cells and CAFs in the neuro-stroma niche. n Schematic diagram of the in vivo orthotopic injection. A cell mixture of CAFs, CFPAC-1, and sNF96.2 cells was injected into mice pancreas, then the mice subjected to MDK inhibitor (iMDK) and interleukin-1 receptor antagonist (IL-1RA) treatment (INHs, inhibitors) or not (n = 5). o–q Photograph (o) and quantification (p, q) of orthotopic tumors of mice. a, c, d, g, k. l Data were the mean ± s.d. of n = 3 independent experiments. i, p, q Data were the mean ± s.d. of n = 5 independent experiments. f, m, n Created with BioRender.com. Statistical analysis: unpaired two-sided t-test (a, c, d, g, i, k, l, p, q); paired two-sided t-test (j). Source data are provided as a Source Data file.

Back to article page