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Glypican-1 identifies cancer exosomes and detects early pancreatic cancer

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  • Sonia A. Melo

    (Metastasis Research Center, University of Texas MD Anderson Cancer Center
    †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.)

  • 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
    National Center for Biotechnology, CNB-CSIC)

  • David Piwnica-Worms

    (The University of Texas M.D. Anderson Cancer Center)

  • Raghu Kalluri

    (Metastasis Research Center, University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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 Reissf, 2015. "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer," Nature, Nature, vol. 523(7559), pages 177-182, July.
    • Handle: RePEc:nat:nature:v:523:y:2015:i:7559:d:10.1038_nature14581
    DOI: 10.1038/nature14581
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    Cited by:

    1. Zhichao Yang & Avijit Mitra & Weisong Liu & Dan Berlowitz & Hong Yu, 2023. "TransformEHR: transformer-based encoder-decoder generative model to enhance prediction of disease outcomes using electronic health records," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Manju Padmasekar & Rajkumar Savai & Werner Seeger & Soni Savai Pullamsetti, 2021. "Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans," IJERPH, MDPI, vol. 18(16), pages 1-20, August.
    3. Ghazala Malik & Fatima Sultan & Ahmed Bin Amir, 2019. "Pancreatic Cancer: Early Detection and Surveillance," Cancer Therapy & Oncology International Journal, Juniper Publishers Inc., vol. 13(1), pages 46-49, January.
    4. Nan Li & Alex Quan & Dan Li & Jiajia Pan & Hua Ren & Gerard Hoeltzel & Natalia Val & Dana Ashworth & Weiming Ni & Jing Zhou & Sean Mackay & Stephen M. Hewitt & Raul Cachau & Mitchell Ho, 2023. "The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Shiyan Dong & Xuan Liu & Ye Bi & Yifan Wang & Abin Antony & DaeYong Lee & Kristin Huntoon & Seongdong Jeong & Yifan Ma & Xuefeng Li & Weiye Deng & Benjamin R. Schrank & Adam J. Grippin & JongHoon Ha &, 2023. "Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Sean L Nguyen & Jacob W Greenberg & Hao Wang & Benjamin W Collaer & Jianrong Wang & Margaret G Petroff, 2019. "Quantifying murine placental extracellular vesicles across gestation and in preterm birth data with tidyNano: A computational framework for analyzing and visualizing nanoparticle data in R," PLOS ONE, Public Library of Science, vol. 14(6), pages 1-14, June.
    7. Joshua D. Spitzberg & Scott Ferguson & Katherine S. Yang & Hannah M. Peterson & Jonathan C. T. Carlson & Ralph Weissleder, 2023. "Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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