Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

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Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

Thursday, 02.07.2015

Authors and Affiliations:

Sonia A. Melo,1, †, * Linda B. Luecke,1, * Christoph Kahlert,1, * Agustin F. Fernandez,2, Seth T. Gammon,3, Judith Kaye,1, Valerie S. LeBleu,1, Elizabeth A. Mittendorf,4, Juergen Weitz,5, Nuh Rahbari,5, Christoph Reissfelder,5, Christian Pilarsky,5, Mario F. Fraga,2, 6, David Piwnica-Worms,3, & Raghu Kalluri,1,

Sónia A. Melo, Linda B. Luecke, Christoph Kahlert, Judith Kaye, Valerie S. LeBleu &, Raghu Kalluri - Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA

Sónia A. Melo - Present address: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal, Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP), 4200 Porto, Portugal

Agustin F. Fernandez & Mario F. Fraga - Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33006 Oviedo, Spain

Seth T. Gammon & David Piwnica-Worms - Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA

Elizabeth A. Mittendorf - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

Juergen Weitz, Nuh Rahbari, Christoph Reissfelder & Christian Pilarsky - Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany

Mario F. Fraga - Department of Immunology and Oncology, National Center for Biotechnology, CNB-CSIC, Cantoblanco, 28049 Madrid, Spain

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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.

 

Journal: Nature

 

Link: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14581.html