Publication Date:
2015-06-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- 5U24-CA126577/CA/NCI NIH HHS/ -- CA-151925/CA/NCI NIH HHS/ -- CA-155370/CA/NCI NIH HHS/ -- CA16672/CA/NCI NIH HHS/ -- DK 081576/DK/NIDDK NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P30-CA016672/CA/NCI NIH HHS/ -- P30CA016672/CA/NCI NIH HHS/ -- P30CA16672/CA/NCI NIH HHS/ -- P50-CA094056/CA/NCI NIH HHS/ -- R01 CA155370/CA/NCI NIH HHS/ -- R01 DK081576/DK/NIDDK NIH HHS/ -- U01 CA151925/CA/NCI NIH HHS/ -- England -- Nature. 2015 Jul 9;523(7559):177-82. doi: 10.1038/nature14581. Epub 2015 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. ; Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33006 Oviedo, Spain. ; Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA. ; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultat Carl Gustav Carus, Technische Universitat Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; 1] Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33006 Oviedo, Spain [2] Department of Immunology and Oncology, National Center for Biotechnology, CNB-CSIC, Cantoblanco, 28049 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26106858" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Biomarkers/blood
;
Cell Line, Tumor
;
Exosomes/genetics/*metabolism
;
Female
;
*Glypicans/blood/metabolism
;
HCT116 Cells
;
Humans
;
MCF-7 Cells
;
Male
;
Mice
;
NIH 3T3 Cells
;
Pancreatic Neoplasms/blood/*diagnosis/pathology
;
Proto-Oncogene Proteins/metabolism
;
ras Proteins/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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