ArticleJournal of extracellular vesicles2022
A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.
Article in Journal of extracellular vesicles, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- The Effects of Extracellular Vesicles From Cancer Cells in Acidosis or ER Stress to Endothelial Cells: Angiogenesis and Endothelial Activation.Biology of the cell · 2026Article
- Extracellular vesicle-derived miRNA-182-5p educates macrophages towards an immunosuppressive phenotype in pancreatic cancer.Signal transduction and targeted therapy · 2026Article
- Innovations in Oncology Diagnostics: Genetic Research and Liquid Biopsy as Tools of Personalised Medicine.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- The Level of a Short Form of Multidrug Resistance-Associated Protein 1 Is Elevated in Plasma Small Extracellular Vesicles Derived From Patients With Pancreatic Ductal Adenocarcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Extracellular vesicles as missiles for enhanced anti-tumor efficacy of oncolytic viruses: from disseminating oncolysis and anti-tumor immunity to targeted delivery.Cell communication and signaling : CCS · 2025Review
- Comparative evaluation of methods for isolating extracellular vesicles from ICC cell culture supernatants: Insights into proteomic and glycomic analysis.Cell communication and signaling : CCS · 2025Article
- Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Tumor-derived extracellular vesicles mediate cell-specific uptake and facilitate enhanced doxorubicin delivery in breast cancer.Frontiers in pharmacology · 2025Article
- Multi-omics analysis of small extracellular vesicles in osteoarthritis: bridging the gap between molecular insights and clinical applications.Burns & trauma · 2025Review
- Tumor-derived exosomes as promising tools for cancer diagnosis and therapy.Frontiers in pharmacology · 2025Review
- A machine-learning approach for pancreatic neoplasia classification based on plasma extracellular vesicles.Frontiers in oncology · 2025Article
- Article
- Comprehensive multi-omics profiling identifies novel molecular subtypes of pancreatic ductal adenocarcinoma.Genes & diseases · 2024Review
- Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma.Journal of extracellular vesicles · 2024Article
- Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy.International journal of molecular sciences · 2024Review
- A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment.International journal of molecular sciences · 2024Review
- Autophagy and the pancreas: Healthy and disease states.Frontiers in cell and developmental biology · 2024Review
- Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients.International journal of molecular sciences · 2023Article
- Article
- Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Although cancer-derived extracellular vesicles (cEVs) are thought to play a pivotal role in promoting cancer progression events, their precise effect on neighbouring normal cells is unknown. In this study, we investigated the impact of pancreatic cancer ductal adenocarcinoma (PDAC) derived EVs on recipient non-tumourigenic pancreatic normal epithelial cells upon internalization. We demonstrate that cEVs are readily internalized and induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in treated normal pancreatic epithelial cells within 24 h. We further show that PDAC cEVs increase cell proliferation, migration, and invasion and that these changes are regulated at least in part, by the UPR mediator DDIT3. Subsequently, these cells release several inflammatory cytokines. Leveraging a layered multi-omics approach, we analysed EV cargo from a panel of six PDAC and two normal pancreas cell lines, using multiple EV isolation methods. We found that cEVs were enriched for an array of biomolecules which can induce or regulate ER stress and the UPR, including palmitic acid, sphingomyelins, metabolic regulators of tRNA charging and proteins which regulate trafficking and degradation. We further show that palmitic acid, at doses relevant to those found in cEVs, is sufficient to induce ER stress in normal pancreas cells. These results suggest that cEV cargo packaging may be designed to disseminate proliferative and invasive characteristics upon internalization by distant recipient normal cells, hitherto unreported. This study is among the first to highlight a major role for PDAC cEVs to induce stress in treated normal pancreas cells that may modulate a systemic response leading to altered phenotypes. These findings highlight the importance of EVs in mediating disease aetiology and open potential areas of investigation toward understanding the role of cEV lipids in promoting cell transformation in the surrounding microenvironment.
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Registered trials
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 OpenQuestion graph.