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Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
Open accessAbstract
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1(+) crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1(+) crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1(+) crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.
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“Of note, in addition to cell-free DNA, recent studies have also shown that detection of nucleic acid cargo within circulating extracellular microvesicles (including exosomes) provides an alternative avenue for assessing the genomic landscape of PDAC.51,52”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [52]
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“Of note, in addition to cell-free DNA, recent studies have also shown that detection of nucleic acid cargo within circulating extracellular microvesicles (including exosomes) provides an alternative avenue for assessing the genomic landscape of PDAC.51,52”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [51]
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Metadata
- Authors
- Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Technische Universität Dresden (DE)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Kalluri, Raghu
- ORCID
- Venue
- Nature
- Published
- 2015-06-24
- Volume
- 523
- Issue
- 7559
- Pages
- 177-182
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4825698
- OpenAlex
- W1500925570
- Cited by
- 2,880
- References
- 63
- Citations by year
- 2026: 129 · 2025: 200 · 2024: 253 · 2023: 305 · 2022: 277 · 2021: 371 · 2020: 320 · 2019: 271 · 2018: 269 · 2017: 234 · 2016: 195 · 2015: 52
- FWCI
- 108.75
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-10-05)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (5u24ca126577-05)
- National Cancer Institute (P30CA16672, U01CA151925, CA-16672, U24-CA-126577, P50CA094056, 5U24CA126577, R01CA155370, CA 155370, CA 151925, P30CA016672)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 081576, R01DK081576)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- glypican-1, tumor-derived exosomes, extracellular vesicles, pancreatic cancer, early cancer detection, circulating exosomes, cell surface proteoglycans, KRAS mutation, non-invasive biomarkers, tumor burden
- MeSH terms
- Animals, Female, Humans, Male, Pancreatic Neoplasms, Proto-Oncogene Proteins, Biomarkers, Proto-Oncogene Proteins p21(ras), ras Proteins, NIH 3T3 Cells, HCT116 Cells, Cell Line, Tumor, Mice, Glypicans, Exosomes, MCF-7 Cells
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