Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice

Author:

Albrengues Jean1ORCID,Shields Mario A.1ORCID,Ng David1,Park Chun Gwon23ORCID,Ambrico Alexandra1ORCID,Poindexter Morgan E.4ORCID,Upadhyay Priya4ORCID,Uyeminami Dale L.4ORCID,Pommier Arnaud1ORCID,Küttner Victoria1,Bružas Emilis15ORCID,Maiorino Laura15ORCID,Bautista Carmelita1ORCID,Carmona Ellese M.23,Gimotty Phyllis A.6,Fearon Douglas T.178ORCID,Chang Kenneth1ORCID,Lyons Scott K.1ORCID,Pinkerton Kent E.4ORCID,Trotman Lloyd C.1,Goldberg Michael S.23ORCID,Yeh Johannes T.-H.1ORCID,Egeblad Mikala1ORCID

Affiliation:

1. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

2. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

3. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USA.

4. Center for Health and the Environment, University of California, Davis, Davis, CA 95616, USA.

5. Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA.

6. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

7. Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.

8. Meyer Cancer Center, Weill Cornell Medical College, New York, NY 10021, USA.

Abstract

Waking up in a trap Cancer patients who have undergone successful treatment can experience relapse of their disease years or even decades later. This is because cancer cells that have disseminated beyond the primary tumor site enter a state of dormancy, where they remain viable but not proliferating. Eventually, by mechanisms that are poorly understood, these clinically undetectable cells “wake up” and form actively growing metastases. Studying mouse models, Albrengues et al. found that sustained lung inflammation and the accompanying formation of neutrophil extracellular traps (NETs) could convert dormant cancer cells to aggressive lung metastases (see the Perspective by Aguirre-Ghiso). Awakening of these cells was associated with NET-mediated remodeling of the extracellular matrix and could be prevented by an antibody against the remodeled version of a matrix protein called laminin-111. Science , this issue p. eaao4227 ; see also p. 1314

Funder

U.S. Department of Defense

National Cancer Institute

Susan G. Komen for the Cure

European Molecular Biology Organization

Lustgarten Foundation

Association pour la Recherche sur le Cancer

northwell health

Cold Spring Harbor Laboratory Cancer Center Support Grant

Deutsche Forschungsgemeinschaft

George A. and Marjorie H. Anderson Fellowship from the Watson School

R01 NIH Research Grant Program

Terri Brodeur Breast Cancer Foundation

Starr Centennial Scholarship from the Watson School of Biological Sciences

Cold Sprint Harbor Laboratory Cancer Center Grant

Cold Spring Harbor Laboratory Cancer Center Grant

Cedar Hill Foundation

Boehringer Ingelheim Fonds Ph.D. fellowship

AACR-Bayer Healthcare Basic Cancer Research Fellowship

R01 NIH Research Grant

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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4. Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-gamma in establishing and maintaining the tumor-dormant state;Farrar J. D.;J. Immunol.,1999

5. EblacZ tumor dormancy in bone marrow and lymph nodes: Active control of proliferating tumor cells by CD8+ immune T cells;Müller M.;Cancer Res.,1998

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