Cited by 2,880Extracellular vesicles in diseaseCancer Genomics and DiagnosticsPancreatic and Hepatic Oncology Research

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Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

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Melo, Sonia A., Luecke, Linda B., Kahlert, Christoph, Fernandez, Agustin F., Gammon, Seth T., Kaye, Judith, LeBleu, Valerie S., Mittendorf, Elizabeth A., Weitz, Juergen, Rahbari, Nuh, Reissfelder, Christoph, Pilarsky, Christian, Fraga, Mario F., Piwnica-Worms, David, Kalluri, Raghu·2015·Nature

DOI 10.1038/nature14581PMC PMC4825698

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Abstract

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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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: Kahlert, Christoph
Gammon, Seth T.
LeBleu, Valerie S.
Mittendorf, Elizabeth A.
Rahbari, Nuh
Reissfelder, Christoph
Pilarsky, Christian
Fraga, Mario F.
Piwnica-Worms, David
Kalluri, Raghu
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2015-06-24
Volume: 523
Issue: 7559
Pages: 177-182
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature14581
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

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