ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Research trends and knowledge structure of pancreatic cancer and type 2 diabetes mellitus research: a two-decade CiteSpace analysis.Frontiers in endocrinology · 2026Pooled it
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Extracellular vesicle biomarkers in pancreatic ductal adenocarcinoma: from bulk detection to single-extracellular vesicle profiling and endoscopic liquid biopsy.Journal of gastroenterology · 2026Review
- Esculetin induces apoptosis and functional impairment in INS-1 pancreatic β-cells associated with ER stress and MAPK/JNK signaling.Protoplasma · 2026Article
- Pancreatic Cancer Screening in New-onset and Deteriorating Diabetes: Preliminary Results From the PANDOME Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps.International journal of molecular sciences · 2025Review
- Unraveling the Role of MDK-SDC4 Interaction in Pancreatic Cancer-Associated New-Onset Diabetes by Single-Cell Transcriptomic Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prediction of Pancreatic Cancer Risk in Patients with New-Onset Diabetes.Visceral medicine · 2025Review
- The recent progress of tumor cell-derived exosomes in the pathogenesis, diagnosis and therapeutic strategies of tumors.Journal of translational medicine · 2025Review
- Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease.Diabetes & metabolism journal · 2025Review
- Effect of tumor microenvironment in pancreatic cancer on the loss of β-cell mass: implications for type 3c diabetes.Journal of gastroenterology · 2025Article
- Lipotoxicity Induces β-cell Small Extracellular Vesicle-Mediated β-cell Dysfunction in Male Mice.Endocrinology · 2025Article
- Regulatory Roles of Exosomes in Aging and Aging-Related Diseases.Biogerontology · 2025Review
- New-onset diabetes as an emerging risk group for early detection of pancreatic cancer: current evidence, clinical challenge, and future directions.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Review
- The emerging role of extracellular vesicles in diabetes and complications: mechanistic insights and translational prospects.Frontiers in endocrinology · 2025Review
- The Role of Exosomes in Myocardial Ischemia-Reperfusion Injury.Cardiology · 2025Review
- The role of Caveolin-1 in tumor-derived extracellular vesicle biology and its implications.Frontiers in cell and developmental biology · 2025Review
- Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis.International journal of molecular sciences · 2024Review
- Sorcin can trigger pancreatic cancer-associated new-onset diabetes through the secretion of inflammatory cytokines such as serpin E1 and CCL5.Experimental & molecular medicine · 2024Article
- How does exosome cause diabetes?Hormones (Athens, Greece) · 2024Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
purposePancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. EXPERIMENTAL
methodsWe characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown.
resultsExosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species.
conclusionsPancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into circulation that inhibit insulin secretion, likely through adrenomedullin-induced ER stress and failure of the unfolded protein response.
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What OpenQuestion holds
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.