RRC ID 67182
Author Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, Piwnica-Worms D, Kalluri R.
Title Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
Journal Nature
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.
Volume 523(7559)
Pages 177-82
Published 2015-7-9
DOI 10.1038/nature14581
PII nature14581
PMID 26106858
PMC PMC4825698
MeSH Animals Biomarkers / blood Cell Line, Tumor Exosomes / genetics Exosomes / metabolism* Female Glypicans* / blood Glypicans* / metabolism HCT116 Cells Humans MCF-7 Cells Male Mice NIH 3T3 Cells Pancreatic Neoplasms / blood Pancreatic Neoplasms / diagnosis* Pancreatic Neoplasms / pathology Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins p21(ras) ras Proteins / metabolism
IF 42.779
Human and Animal Cells T3M-4(RCB1021)