Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 8, Issue 361, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aag1711
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Funding
- CSHL Cancer Center Support Grant [5P30CA045508]
- U.S. Department of Defense [W81XWH-14-1-0078]
- Long Island 2-Day Walk to Fight Breast Cancer
- Joni Gladowsky Breast Cancer Foundation
- NIH [5U01CA180944-02]
- Hope Foundation
- Cancer Research Institute CLIP (Clinic and Laboratory Integration Program) Grant
- National Institute of General Medical Sciences Medical Scientist Training Program Training Award [T32-GM008444]
- Aid for Cancer Research
- Boehringer Ingelheim Fonds
- Formacion de Profesorado Universitario fellowship [AP2010-2197]
- National Cancer Institute [K99 CA181490]
- Deutsche Forschungsgemeinschaft research fellowship [KU 3264/1-1]
- Grants-in-Aid for Scientific Research [16K19044] Funding Source: KAKEN
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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 metastasispromoting tumor-host interaction and a potential therapeutic target.
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