ArticleMolecular oncology2019
Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.Molecular cancer · 2025Review
- TGFBI promotes EMT and perineural invasion of pancreatic cancer via PI3K/AKT pathway.Medical oncology (Northwood, London, England) · 2025Article
- Spatial Transcriptomics Reveals Novel Mechanisms Involved in Perineural Invasion in Pancreatic Ductal Adenocarcinomas.Cancers · 2025Article
- Significance and mechanisms of perineural invasion in malignant tumors.Frontiers in oncology · 2025Review
- Neural Circuitries between the Brain and Peripheral Solid Tumors.Cancer research · 2024Review
- Associations of body composition parameters with postoperative outcome and perineural tumour invasion after oncological pancreatic resection.BMC surgery · 2024Article
- Bioinformatics-Based Identification of Key Prognostic Genes in Neuroblastoma with a Focus on Immune Cell Infiltration and Diagnostic Potential of VGF.Pharmacogenomics and personalized medicine · 2024Article
- Investigation of the correlation between AGRN expression and perineural invasion in colon cancer.Frontiers in molecular biosciences · 2024Article
- Gene Expression Array Analyses Predict Proto-Oncogene Expression During Perineural Invasion in Pancreatic Ductal Adenocarcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition.Journal of cancer research and clinical oncology · 2023Article
- Functional and Clinical Proteomic Exploration of Pancreatic Cancer.Molecular & cellular proteomics : MCP · 2023Review
- Global-feature of autoimmune glomerulonephritis using proteomic analysis of laser capture microdissected glomeruli.Frontiers in immunology · 2023Article
- Article
- In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration.International journal of molecular sciences · 2022Article
- Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Nodal Enhances Perineural Invasion in Pancreatic Cancer by Promoting Tumor-Nerve Convergence.Journal of healthcare engineering · 2022Article
- Identification of Angiogenesis-Related Prognostic Biomarkers Associated With Immune Cell Infiltration in Breast Cancer.Frontiers in cell and developmental biology · 2022Article
- Comparison of Gene Expression Profiles of Signet Ring Cell Carcinoma and Poorly Cohesive Carcinoma in Early Gastric Cancer.Clinical Medicine Insights. Oncology · 2022Article
- Nerve Growth Factor (NGF) Encourages the Neuroinvasive Potential of Pancreatic Cancer Cells by Activating the Warburg Effect and Promoting Tumor Derived Exosomal miRNA-21 Expression.Oxidative medicine and cellular longevity · 2022Article
- Discovery of NEU1 as a candidatedone. renal biomarker for proliferative lupus nephritis chronicity.Lupus science & medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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 PC12 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 SCG2 (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 PC12 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 (GAP43), closely recapitulated our proteomic findings in PDAC tissues. Furthermore, induction of VGF, while not necessary for PC12 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.