ArticleCellular and molecular life sciences : CMLS2017
PAP/REG3A favors perineural invasion in pancreatic adenocarcinoma and serves as a prognostic marker.
Article in Cellular and molecular life sciences : CMLS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Synergistic effects of PAR2 and TrkA exacerbate visceral hypersensitivity induced by chronic pancreatitis in rats.IBRO neuroscience reports · 2025Article
- REG3A: A Multifunctional Antioxidant Lectin at the Crossroads of Microbiota Regulation, Inflammation, and Cancer.Cancers · 2025Review
- Review
- REG3A secreted by peritumoral acinar cells enhances pancreatic ductal adenocarcinoma progression via activation of EGFR signaling.Cell communication and signaling : CCS · 2025Article
- Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients.The journal of pain · 2025Article
- A Novel In Vitro Pathological Model for Studying Neural Invasion in Non-Melanoma Skin Cancer.Gels (Basel, Switzerland) · 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
- Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions.Frontiers in oncology · 2024Review
- Unraveling the Mysteries of Perineural Invasion in Benign and Malignant Conditions.Current oncology (Toronto, Ont.) · 2023Review
- Predicting response to immunotherapy in gastric cancer via assessing perineural invasion-mediated inflammation in tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2023Article
- Comprehensive analysis of LILR family genes expression and tumour-infiltrating immune cells in early-stage pancreatic ductal adenocarcinoma.IET systems biology · 2023Article
- A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells.Cancers · 2022Article
- The regenerating protein 3A: a crucial molecular with dual roles in cancer.Molecular biology reports · 2022Review
- Nodal Enhances Perineural Invasion in Pancreatic Cancer by Promoting Tumor-Nerve Convergence.Journal of healthcare engineering · 2022Article
- REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.Communications biology · 2021Article
- Re-expression of REG family and DUOXs genes in CRC organoids by co-culturing with CAFs.Scientific reports · 2021Article
- Inhibition of Mast Cell Degranulation Relieves Visceral Hypersensitivity Induced by Pancreatic Carcinoma in Mice.Journal of molecular neuroscience : MN · 2019Article
- Role of Regenerating Islet-Derived Protein 3A in Gastrointestinal Cancer.Frontiers in oncology · 2019Review
- Update on current pancreatic treatments: from molecular pathways to treatment.Journal of Cancer · 2019Review
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer. First, we demonstrated that, in PDA, PAP/REG3A is produced by inflamed acinar cells from the peritumoral microenvironment and then enhances the migratory and invasive abilities of cancer cells. More specifically, using perineural ex vivo assays we revealed that PAP/REG3A favors PNI through activation of the JAK/STAT signaling pathway in cancer cells. Finally, we analyzed the level of PAP/REG3A in blood from healthy donors or patients with PDA from three independent cohorts. Patients with high levels of PAP/REG3A had overall shorter survival as well as poor surgical outcomes with reduced disease-free survival. Our study provides a rationale for using the PAP/REG3A level as a biomarker to improve pancreatic cancer prognosis. It also suggests that therapeutic targeting of PAP/REG3A activity in PDA could limit tumor cell aggressiveness and PNI.
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