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)
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 Cancer Center Program > Signal Transduction CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Shared Resources > Animal Shared Resource CSHL labs > Egeblad lab School of Biological Sciences > Publications |
| Depositing User: | Matt Covey |
| Date: | 19 October 2016 |
| Date Deposited: | 14 Nov 2016 21:20 |
| Last Modified: | 08 Jul 2021 15:30 |
| PMCID: | PMC5550900 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33898 |
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