Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis

Mélanie Demers, Daniela S. Krause, Daphne Schatzberg, Kimberly Martinod, Jaymie R. Voorhees, Tobias A. Fuchs, David T. Scadden, and Denisa D. Wagner
PNAS August 7, 2012 109 (32) 13076-13081; https://doi.org/10.1073/pnas.1200419109
Mélanie Demers
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
cDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniela S. Krause
dCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114; and
eDepartment of Pathology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daphne Schatzberg
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kimberly Martinod
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
fGraduate Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaymie R. Voorhees
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tobias A. Fuchs
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
cDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David T. Scadden
dCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Denisa D. Wagner
aImmune Disease Institute, Boston, MA 02115;
bProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115;
cDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wagner@idi.harvard.edu
  1. Edited by Napoleone Ferrara, Genentech, Inc., South San Francisco, CA, and approved June 28, 2012 (received for review January 10, 2012)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Abstract

Cancer-associated thrombosis often lacks a clear etiology. However, it is linked to a poor prognosis and represents the second-leading cause of death in cancer patients. Recent studies have shown that chromatin released into blood, through the generation of neutrophil extracellular traps (NETs), is procoagulant and prothrombotic. Using a murine model of chronic myelogenous leukemia, we show that malignant and nonmalignant neutrophils are more prone to NET formation. This increased sensitivity toward NET generation is also observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutrophils, which are predisposed to NET formation. In addition, in the late stages of the breast carcinoma model, NETosis occurs concomitant with the appearance of venous thrombi in the lung. Moreover, simulation of a minor systemic infection in tumor-bearing, but not control, mice results in the release of large quantities of chromatin and a prothrombotic state. The increase in neutrophil count and their priming is mediated by granulocyte colony-stimulating factor (G-CSF), which accumulates in the blood of tumor-bearing mice. The prothrombotic state in cancer can be reproduced by treating mice with G-CSF combined with low-dose LPS and leads to thrombocytopenia and microthrombosis. Taken together, our results identify extracellular chromatin released through NET formation as a cause for cancer-associated thrombosis and unveil a target in the effort to decrease the incidence of thrombosis in cancer patients.

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: wagner{at}idi.harvard.edu.
  • Author contributions: M.D., D.S.K., D.T.S., and D.D.W. designed research; M.D., D.S.K., D.S., K.M., J.R.V., and T.A.F. performed research; M.D., D.S.K., D.S., K.M., J.R.V., and D.D.W. analyzed data; and M.D. and D.D.W. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200419109/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Cancer promotes NET formation
Mélanie Demers, Daniela S. Krause, Daphne Schatzberg, Kimberly Martinod, Jaymie R. Voorhees, Tobias A. Fuchs, David T. Scadden, Denisa D. Wagner
Proceedings of the National Academy of Sciences Aug 2012, 109 (32) 13076-13081; DOI: 10.1073/pnas.1200419109

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Cancer promotes NET formation
Mélanie Demers, Daniela S. Krause, Daphne Schatzberg, Kimberly Martinod, Jaymie R. Voorhees, Tobias A. Fuchs, David T. Scadden, Denisa D. Wagner
Proceedings of the National Academy of Sciences Aug 2012, 109 (32) 13076-13081; DOI: 10.1073/pnas.1200419109
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 109 (32)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Medical Sciences

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Scientist looking at an electronic tablet
Opinion: Standardizing gene product nomenclature—a call to action
Biomedical communities and journals need to standardize nomenclature of gene products to enhance accuracy in scientific and public communication.
Image credit: Shutterstock/greenbutterfly.
One red and one yellow modeled protein structures
Journal Club: Study reveals evolutionary origins of fold-switching protein
Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years.
Image credit: Acacia Dishman/Medical College of Wisconsin.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490