Fig. 6
PGE2 promotes the secretion of LIF and ADAMTS-1 from SCs to drive PNI development. a After RSC96 cells were treated with PGE2, PANC-1, or BxPC-3, RNA-seq differential gene intersection analysis was performed to identify commonly upregulated genes; LIF and ADAMTS-1 were found to be associated with PNI (n = 3). b, c RT‒qPCR was conducted to assess the effects of treatment and pancreatic cancer cell coculture on LIF mRNA expression in RSC96 and sNF96.2 cells (n = 3). d, e RT‒qPCR analysis was used to determine the effect of PGE2 (0 nM, 0.1 nM, 1 nM, or 10 nM) treatment on LIF mRNA expression in RSC96 and sNF96.2 cells (n = 3). f, g Protein expression levels of ADAMTS-1 in RSC96 cells cocultured with PANC-1 or BxPC-3 cells (n = 3). h, i Protein expression levels of ADAMTS-1 in RSC96 cells treated with PGE2 (0 nM, 0.1 nM, 1 nM, or 10 nM) (n = 3). l, m Protein expression levels of ADAMTS-1 in sNF96.2 cells cocultured with PANC-1 or BxPC-3 cells (n = 3). n, o Protein expression levels of ADAMTS-1 in sNF96.2 cells treated with PGE2 (0 nM, 0.1 nM, 1 nM, or 10 nM) (n = 3). j, k, p, q Protein expression levels of ADAMTS-1 in sNF96.2 cells (cocultured with BxPC-3/PANC-1) following CAY10526 treatment and PGE2 supplementation (n = 3). r, u Effect of a LIF neutralizing antibody on DRG axon growth (n = 3). Scale bar: 200 μm. s, t, v, w Effect of LIF neutralizing antibody on PNI in the PANC-1/BxPC-3-RSC96 coculture system (n = 3). Scale bar=100 μm. x Schematic diagram illustrating the mechanism: pancreatic cancer-derived PTGES/PGE2 promotes SC dedifferentiation and the secretion of LIF and ADAMTS-1, thereby inducing PNI. This image was created with Adobe Illustrator. All the results are presented as the means ± SDs. Each data point in the bar graphs represents an individual sample. All statistical significance was determined by one-way analysis of variance followed by Tukey’s HSD post hoc test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001
