ArticleBritish journal of cancer2017
Exosomes confer chemoresistance to pancreatic cancer cells by promoting ROS detoxification and miR-155-mediated suppression of key gemcitabine-metabolising enzyme, DCK.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.
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Who cites it
169 citing papers in PubMed, 255 citations in OpenAlex.
- The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals.bioRxiv : the preprint server for biology · 2026Article
- Extracellular vesicle biomarkers in pancreatic ductal adenocarcinoma: from bulk detection to single-extracellular vesicle profiling and endoscopic liquid biopsy.Journal of gastroenterology · 2026Review
- Extracellular Vesicles in Cancer: Biomarkers, Mechanisms, and Emerging Diagnostic Technologies.Advanced healthcare materials · 2026Review
- Harnessing tumor-associated exosomal aminopeptidase N as a dual-function tool for monitoring and tackling chemoresistance in gastric cancer.Cell communication and signaling : CCS · 2026Article
- Engineering Viral Surface Antigens to Improve Display on Virus-like Particle (VLP) Vaccine Prototypes.Biotech (Basel (Switzerland)) · 2026Article
- Review
- Exosomal Cargoes Derived from Neural Stem Cell: A New Strategy of Parkinson's Disease Treatment.Molecular neurobiology · 2026Review
- miR-155 aberrant expression impairs tumor rejection because of its targeting of ICOSL and multiple pathways implicated in the antitumor response.Pharmacological reviews · 2026Review
- Metabolic reprogramming and plasticity of cancer stem cells.Frontiers in cell and developmental biology · 2026Review
- Research on exosomes in cancer multidrug resistance and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.Journal of extracellular vesicles · 2025Article
- Effect of a 12-Week Endurance Training Program on Circulating Extracellular Vesicle Proteome in Sedentary Adults With Obesity.Journal of extracellular biology · 2025Article
- Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs.Clinical and translational medicine · 2025Review
- Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Exploring extracellular RNA as drivers of chemotherapy resistance in cancer.Molecular biology reports · 2025Review
- Exosomal microRNAs: impact on cancer detection, treatment, and monitoring.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle.Cell biology and toxicology · 2024Review
- Progress of Exosomal LncRNAs in Pancreatic Cancer.International journal of molecular sciences · 2024Review
- Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.Molecular cancer · 2024Article
109 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChemoresistance is a significant clinical problem in pancreatic cancer (PC) and underlying molecular mechanisms still remain to be completely understood. Here we report a novel exosome-mediated mechanism of drug-induced acquired chemoresistance in PC cells.
methodsDifferential ultracentrifugation was performed to isolate extracellular vesicles (EVs) based on their size from vehicle- or gemcitabine-treated PC cells. Extracellular vesicles size and subtypes were determined by dynamic light scattering and marker profiling, respectively. Gene expression was examined by qRT-PCR and/or immunoblot analyses, and direct targeting of DCK by miR-155 was confirmed by dual-luciferase 3'-UTR reporter assay. Flow cytometry was performed to examine the apoptosis indices and reactive oxygen species (ROS) levels in PC cells using specific dyes. Cell viability was determined using the WST-1 assay.
resultsConditioned media (CM) from gemcitabine-treated PC cells (Gem-CM) provided significant chemoprotection to subsequent gemcitabine toxicity and most of the chemoresistance conferred by Gem-CM resulted from its EVs fraction. Sub-fractionation grouped EVs into distinct subtypes based on size distribution and marker profiles, and exosome (Gem-Exo) was the only sub-fraction that imparted chemoresistance. Gene expression analyses demonstrated upregulation of SOD2 and CAT (ROS-detoxifying genes), and downregulation of DCK (gemcitabine-metabolising gene) in Gem-Exo-treated cells. SOD/CAT upregulation resulted, at least in part, from exosome-mediated transfer of their transcripts and they suppressed basal and gemcitabine-induced ROS production, and partly promoted chemoresistance. DCK downregulation occurred through exosome-delivered miR-155 and either the functional suppression of miR-155 or restoration of DCK led to marked abrogation of Gem-Exo-mediated chemoresistance.
conclusionsTogether, these findings establish a novel role of exosomes in mediating the acquired chemoresistance of PC.
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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 OpenQuestion graph.