Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Next-Generation Sequencing in Medicine (Upcoming)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact

NETing cancer cells


Surgical resection is a primary treatment for many solid tumors; however, patients frequently develop post-surgical infections, which are associated with adverse oncologic outcomes. Jonathan Cools-Lartigue and colleagues examined the role of infection-responsive neutrophils in post-surgical cancer progression. Post-surgery, there is an increase in the number of circulating neutrophils, which play a role in pathogen elimination. Cools-Lartigue and colleagues found that circulating cancer cells become entrapped in neutrophil extracellular traps (NETs), DNA webs that are released from neutrophils in response to inflammation. Using a murine model of post-surgical infection, they found that NET trapping was associated with increased metastatic burden; treatment with NET inhibitors decreased metastases. These findings demonstrate that NETs play a role in metastasis and indicate that NET-targeting therapeutics could potentially reduce post-surgical metastasis. The accompanying immunofluorescent microscopy image shows accumulation of cancer cells (green) in the hepatic sinusoids (red) after sham surgery, surgery that induced an infection, and infection-inducing surgery in the presence of a NET inhibitor.  

Published July 1, 2013, by Jillian Hurst

Scientific Show Stopper

Related articles

Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Jonathan Cools-Lartigue, … , Paul Kubes, Lorenzo Ferri
Jonathan Cools-Lartigue, … , Paul Kubes, Lorenzo Ferri
Published July 1, 2013
Citation Information: J Clin Invest. 2013;123(8):3446-3458. https://doi.org/10.1172/JCI67484.
View: Text | PDF
Research Article Oncology

Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis

  • Text
  • PDF
Abstract

The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.

Authors

Jonathan Cools-Lartigue, Jonathan Spicer, Braedon McDonald, Stephen Gowing, Simon Chow, Betty Giannias, France Bourdeau, Paul Kubes, Lorenzo Ferri

×
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts