Journal: Signal Transduction and Targeted Therapy

Article Title: Prostaglandin E 2 -driven dedifferentiation of Schwann cells leads to perineural invasion in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-026-02648-x

Figure Lengend Snippet: SCs are enriched in the PNI-positive region. a Schematic diagram of the workflow; some of the graphical elements were created wtith BioGDP. b Division of perineural invasion regions (PNI-region: PNI, PNI-near, PNI-mid, PNI-away) and nonperineural invasion regions (NPNI: NPNI, NPNI-near, NPNI-mid, NPNI-away) in representative spatial transcriptomic images of PDAC PNI samples, with corresponding representative HE-stained images of spot points (right) (n = 4). N: Nerve, T: Tumor. Scale bar: 500 μm. c GSVA of the PNI region and the NPNI region. d Correlations between different cell types and the expression levels of marker genes. e Cell type distribution scatter plot based on the UMAP dimensionality reduction algorithm; f UMAP plot of SC subsets in pancreatic cancer tissues. g Feature score of nomyelinating SCs at the single-cell level in each of the two SC subsets ( p = 0.025). h Representative images of RCTD single-cell mapping results based on PNI regions and NPNI regions (n = 4); i Stacked bar charts of different PNI regions and NPNI regions, showing the proportions of various cell types in different samples. j , k Representative mIHC images of human normal pancreatic tissues, PDAC-PNI- tissues, and PDAC-PNI+ tissues stained with PGP9.5, SOX2, c-Jun, and MUC1 antibodies. Scale bar: 100 μm (left), 50 μm (right). The ratios of SOX2+ and c-Jun+ positive cells in normal pancreatic tissues, PDAC-PNI- tissues, and PDAC-PNI+ tissues ( n = 5). All the results are presented as the means ± SDs. Each data point in the bar graphs represents an individual sample. Statistical significance was determined by a two-tailed unpaired t test (Fig. 1g) and one-way analysis of variance followed by Tukey’s HSD post hoc test (Fig. 1j). **** p < 0.0001

Article Snippet: For mIHC staining, formalin-fixed sections were stained with antibodies against PGP9.5 (1:200, Abways, CY6722), MUC1 (1:200, BOSTER, BM4548), SOX2 (1:200, Diagbio, db16528), c-Jun (1:200, Selleck, F0168), and p75NTR (1:200, ABclonal, A11169) according to the manufacturer’s instructions for the multicolor immunofluorescence kit (Zolgene, PR-004507) and imaged with a KFbio Pathology Imaging System (KF-FL-005).

Techniques: Staining, Expressing, Marker, Single Cell, Two Tailed Test

Journal: Signal Transduction and Targeted Therapy

Article Title: Prostaglandin E 2 -driven dedifferentiation of Schwann cells leads to perineural invasion in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-026-02648-x

Figure Lengend Snippet: Pancreatic cancer cells promote SC dedifferentiation. a Schematic diagram of the coculture system of PDAC cells and SCs. b Venn diagram of upregulated pathways in RSC96 (+PANC-1) cells and RSC96 (+BxPC-3) cells compared with RSC96 cells ( n = 3). c , e Transwell assays were used to evaluate the effects of PANC-1 and BxPC-3 cells on the migration of sNF96.2 cells ( n = 6). Scale bar: 100 μm. d Microscopy images showing the morphological changes in sNF96.2 cells induced by PANC-1 and BxPC-3 cells. Scale bars: 50 μm (upper panels) and 20 μm (lower panels). f – j Western blotting was performed to detect the protein expression levels of dedifferentiation markers (p75NTR, c-Jun, SOX2, N-cadherin, and GDNF) in sNF96.2 cells after coculture with PANC-1 or BxPC-3 cells ( n = 3). k , m Transwell assays were used to assess the effects of PANC-1 and BxPC-3 cells on the migration of RSC96 cells ( n = 6). Scale bar: 100 μm. l Microscopy images showing the morphological changes in RSC96 cells induced by PANC-1 and BxPC-3 cells. Scale bars: 50 μm (upper panels) and 20 μm (lower panels). n – r Western blotting was conducted to determine the protein expression levels of dedifferentiation markers (p75NTR, c-Jun, SOX2, N-cadherin, and GDNF) in RSC96 cells after coculture with PANC-1 or BxPC-3 cells (n = 3). Relative expression levels were quantified as p75NTR/GAPDH, c-Jun/GAPDH and GDNF/GAPDH; since the molecular weight of SOX2 (~35 kDa) is close to that of GAPDH (~36 kDa), SOX2/β-actin was used for relative expression quantification. All the results are presented as the means ± SDs. Each data point in the bar graphs represents an individual sample. 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

Article Snippet: For mIHC staining, formalin-fixed sections were stained with antibodies against PGP9.5 (1:200, Abways, CY6722), MUC1 (1:200, BOSTER, BM4548), SOX2 (1:200, Diagbio, db16528), c-Jun (1:200, Selleck, F0168), and p75NTR (1:200, ABclonal, A11169) according to the manufacturer’s instructions for the multicolor immunofluorescence kit (Zolgene, PR-004507) and imaged with a KFbio Pathology Imaging System (KF-FL-005).

Techniques: Migration, Microscopy, Western Blot, Expressing, Molecular Weight

Journal: Signal Transduction and Targeted Therapy

Article Title: Prostaglandin E 2 -driven dedifferentiation of Schwann cells leads to perineural invasion in pancreatic ductal adenocarcinoma

doi: 10.1038/s41392-026-02648-x

Figure Lengend Snippet: Pancreatic cancer-derived PGE 2 induces SC activation. a Representative IF images of DiI and PTGER1/2/4 in RSC96 cells. Scale bars: 20 μm (left), 5 μm (right). b Representative F-actin IF images of RSC96 and sNF96.2 cells after treatment with different doses of PGE 2 (0 nM, 0.1 nM, 1 nM, or 10 nM). Scale bar: 50 μm. c , e – g Protein expression levels of p75NTR, c-Jun, and SOX2 in RSC96 cells treated with different doses of PGE 2 (0 nM, 0.1 nM, 1 nM, or 10 nM). Relative expression levels were quantified as p75NTR/GAPDH and c-Jun/GAPDH; since the molecular weight of SOX2 (~35 kDa) is close to that of GAPDH (~36 kDa), the relative expression of SOX2/β-actin was quantified ( n = 3). d , h – j Representative IF images of p75NTR, c-Jun, and SOX2 in RSC96 cells after PGE 2 intervention. Scale bar: 100 μm. Statistics of the relative fluorescence intensity between the control and treatment groups are shown ( n = 3). k , o - q Protein expression levels of p75NTR, c-Jun, and SOX2 in RSC96 cells (RSC96-PANC-1 coculture system) following CAY10526 treatment and PGE 2 supplementation ( n = 3). l , r–t Protein expression levels of p75NTR, c-Jun, and SOX2 in RSC96 cells (RSC96-BxPC-3 coculture system) following CAY10526 treatment and PGE 2 supplementation ( n = 3). m Effects of CAY10526 treatment and PGE 2 supplementation on 3D cocultures of RSC96 cells with HPNE, PANC-1 or BxPC-3 cells ( n = 3).Scale bar: 200 μm. +B/P/H: +BxPC-3/PANC-1/HPNE, + DMSO:+BxPC-3/PANC-1/HPNE + DMSO, + CAY:+BxPC-3/PANC-1/HPNE + DMSO + CAY10526, + CAY + PGE 2 :+BxPC-3/PANC-1/HPNE + DMSO + CAY10526 + PGE 2 . n , u , v effects of CAY10526 treatment and PGE 2 supplementation on PANC-1/BxPC-3-DRG cocultures, along with quantification of the DRG growth index ( n = 3). Scale bar: 500 μm. +B/P: +BxPC-3/PANC-1, +DMSO: +BxPC-3/PANC-1 + DMSO, +CAY: +BxPC-3/PANC-1 + DMSO + CAY10526, +CAY+. PGE 2 : +BxPC-3/PANC-1 + DMSO + CAY10526 + PGE 2. All the results are presented as the means ± SDs. Each data point in the bar graphs represents an individual sample. Statistical significance was determined by one-way analysis of variance followed by Tukey’s HSD post hoc test (for e – g , o – t , and u , v ) and a two-tailed unpaired t test (for Fig. 5h-j). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: For mIHC staining, formalin-fixed sections were stained with antibodies against PGP9.5 (1:200, Abways, CY6722), MUC1 (1:200, BOSTER, BM4548), SOX2 (1:200, Diagbio, db16528), c-Jun (1:200, Selleck, F0168), and p75NTR (1:200, ABclonal, A11169) according to the manufacturer’s instructions for the multicolor immunofluorescence kit (Zolgene, PR-004507) and imaged with a KFbio Pathology Imaging System (KF-FL-005).

Techniques: Derivative Assay, Activation Assay, Expressing, Molecular Weight, Fluorescence, Control, Two Tailed Test