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• W2913636745 abstract "Perineural invasion ( PNI ) is a common and characteristic feature of pancreatic ductal adenocarcinoma ( PDAC ) that is associated with poor prognosis, tumor recurrence, and generation of pain. However, the molecular alterations in cancer cells and nerves within PNI have not previously been comprehensively analyzed. Here, we describe our proteomic analysis of the molecular changes underlying neuro‐epithelial interactions in PNI using liquid chromatography–mass spectrometry ( LC ‐ MS / MS ) in microdissected PNI and non‐ PNI cancer, as well as in invaded and noninvaded nerves from formalin‐fixed, paraffin‐embedded PDAC tissues. In addition, an in vitro model of PNI was developed using a co‐culture system comprising PDAC cell lines and PC 12 cells as the neuronal element. The overall proteomic profiles of PNI and non‐ PNI cancer appeared largely similar. In contrast, upon invasion by cancer cells, nerves demonstrated widespread plasticity with a pattern consistent with neuronal injury. The up‐regulation of SCG 2 (secretogranin II ) and neurosecretory protein VGF (nonacronymic) in invaded nerves in PDAC tissues was further validated using immunohistochemistry. The tested PDAC cell lines were found to be able to induce neuronal plasticity in PC 12 cells in our in vitro established co‐culture model. Changes in expression levels of VGF , as well as of two additional proteins previously reported to be overexpressed in PNI , Nestin and Neuromodulin ( GAP 43), closely recapitulated our proteomic findings in PDAC tissues. Furthermore, induction of VGF , while not necessary for PC 12 survival, mediated neurite extension induced by PDAC cell lines. In summary, here we report the proteomic alterations underlying PNI in PDAC and confirm that PDAC cells are able to induce neuronal plasticity. In addition, we describe a novel, simple, and easily adaptable co‐culture model for in vitro study of neuro‐epithelial interactions." @default.
• W2913636745 created "2019-02-21" @default.
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• W2913636745 date "2019-03-05" @default.
• W2913636745 modified "2023-10-14" @default.
• W2913636745 title "Perineural invasion in pancreatic cancer: proteomic analysis and <i>in vitro</i> modelling" @default.
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• W2913636745 doi "https://doi.org/10.1002/1878-0261.12463" @default.
• W2913636745 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6487729" @default.
• W2913636745 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30690892" @default.
• W2913636745 hasPublicationYear "2019" @default.
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