title: Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.
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.
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Melo
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Luecke
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.affiliation: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Agustin F
authors.initials: AF
authors.lastname: Fernandez
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Gammon
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Kaye
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: LeBleu
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.affiliation: Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Weitz
authors.affiliation: Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Nuh
authors.initials: N
authors.lastname: Rahbari
authors.affiliation: Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reissfelder
authors.affiliation: Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.affiliation: 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.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.affiliation: Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D053673:Glypicans / Q000097:blood / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053673:Glypicans; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins