Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps

Park, J., Wysocki, R. W., Amoozgar, Z., Maiorino, L., Fein, M. R., Jorns, J., Schott, A. F., Kinugasa-Katayama, Y., Lee, Y., Won, N. H., Nakasone, E. S., Hearn, S. A., Kuttner, V., Qiu, J., Almeida, A. S., Perurena, N., Kessenbrock, K., Goldberg, M. S., Egeblad, M. (October 2016) Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med, 8 (361). 361ra138. ISSN 1946-6242 (Electronic)1946-6234 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/27798263
DOI: 10.1126/scitranslmed.aag1711

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > metastasis
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Watson School > Publications
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 19 October 2016
Date Deposited: 14 Nov 2016 21:20
Last Modified: 05 Mar 2018 20:47
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33898

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