Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

Sonia A. Melo, Linda B. Luecke, Christoph Kahlert, Agustin F. Fernandez, Seth T. Gammon, Judith Kaye, Valerie S. LeBleu, Elizabeth A. Mittendorf, Juergen Weitz, Nuh Rahbari, Christoph Reissfelder, Christian Pilarsky, Mario F. Fraga, David Piwnica-Worms and Raghu Kalluri ()
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Sonia A. Melo: Metastasis Research Center, University of Texas MD Anderson Cancer Center
Linda B. Luecke: Metastasis Research Center, University of Texas MD Anderson Cancer Center
Christoph Kahlert: Metastasis Research Center, University of Texas MD Anderson Cancer Center
Agustin F. Fernandez: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo
Seth T. Gammon: The University of Texas M.D. Anderson Cancer Center
Judith Kaye: Metastasis Research Center, University of Texas MD Anderson Cancer Center
Valerie S. LeBleu: Metastasis Research Center, University of Texas MD Anderson Cancer Center
Elizabeth A. Mittendorf: The University of Texas MD Anderson Cancer Center
Juergen Weitz: Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
Nuh Rahbari: Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
Christoph Reissfelder: Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
Christian Pilarsky: Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
Mario F. Fraga: Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo
David Piwnica-Worms: The University of Texas M.D. Anderson Cancer Center
Raghu Kalluri: Metastasis Research Center, University of Texas MD Anderson Cancer Center

Nature, 2015, vol. 523, issue 7559, 177-182

Abstract: 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.

Date: 2015
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DOI: 10.1038/nature14581

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