IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-20982-2.html
   My bibliography  Save this article

Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth

Author

Listed:
  • Hafsa Munir

    (University of Cambridge)

  • James O. Jones

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus)

  • Tobias Janowitz

    (Cold Spring Harbor Laboratory, Cold Spring Harbor
    Northwell Health Cancer Institute
    University of Cambridge, Li Ka Shing Centre)

  • Markus Hoffmann

    (Friedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3)

  • Maximilien Euler

    (Friedrich Alexander University Erlangen-Nuremberg, Universitätsklinikum Erlangen, Department of Medicine 3)

  • Carla P. Martins

    (University of Cambridge
    Oncology R&D, AstraZeneca)

  • Sarah J. Welsh

    (Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus
    University of Cambridge, Li Ka Shing Centre)

  • Jacqueline D. Shields

    (University of Cambridge)

Abstract

Tumors consist of cancer cells and a network of non-cancerous stroma. Cancer-associated fibroblasts (CAF) are known to support tumorigenesis, and are emerging as immune modulators. Neutrophils release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NET). Here we show that CAFs induce NET formation within the tumor and systemically in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on CAF-derived Amyloid β, a peptide implicated in both neurodegenerative and inflammatory disorders. Inhibition of NETosis in murine tumors skews neutrophils to an anti-tumor phenotype, preventing tumor growth; reciprocally, t-NETs enhance CAF activation. Mirroring observations in mice, CAFs are detected juxtaposed to NETs in human melanoma and pancreatic adenocarcinoma, and show elevated amyloid and β-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.

Suggested Citation

  • Hafsa Munir & James O. Jones & Tobias Janowitz & Markus Hoffmann & Maximilien Euler & Carla P. Martins & Sarah J. Welsh & Jacqueline D. Shields, 2021. "Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20982-2
    DOI: 10.1038/s41467-021-20982-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-20982-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-20982-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20982-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.