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Sci Transl Med. 2016 Oct 19;8(361):361ra138.

Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps.

Author information

1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
2
Medical Scientist Training Program, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
3
Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
4
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
5
Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA.
6
University of Michigan, Ann Arbor, MI 48109, USA.
7
Department of Pathology, Korea University Anam Hospital, Seoul, South Korea.
8
Cold Spring Harbor Laboratory Cancer Center, NCI Shared Resources and St. Giles Foundation Advanced Microscopy Center, Cold Spring Harbor, NY 11724, USA.
9
University of California, Irvine, Irvine, CA 92697, USA.
10
Department of Microbiology and Immunobiology at Harvard Medical School, Boston, MA 02115, USA.
11
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. egeblad@cshl.edu.

Abstract

Neutrophils, the most abundant type of leukocytes in blood, can form neutrophil extracellular traps (NETs). These are pathogen-trapping structures generated by expulsion of the neutrophil's DNA with associated proteolytic enzymes. NETs produced by infection can promote cancer metastasis. We show that metastatic breast cancer cells can induce neutrophils to form metastasis-supporting NETs in the absence of infection. Using intravital imaging, we observed NET-like structures around metastatic 4T1 cancer cells that had reached the lungs of mice. We also found NETs in clinical samples of triple-negative human breast cancer. The formation of NETs stimulated the invasion and migration of breast cancer cells in vitro. Inhibiting NET formation or digesting NETs with deoxyribonuclease I (DNase I) blocked these processes. Treatment with NET-digesting, DNase I-coated nanoparticles markedly reduced lung metastases in mice. Our data suggest that induction of NETs by cancer cells is a previously unidentified metastasis-promoting tumor-host interaction and a potential therapeutic target.

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PMID:
27798263
PMCID:
PMC5550900
DOI:
10.1126/scitranslmed.aag1711
[Indexed for MEDLINE]
Free PMC Article

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