Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps

Juwon Park, Robert W. Wysocki, Zohreh Amoozgar, Laura Maiorino, Miriam R. Fein, Julie Jorns, Anne F. Schott, Yumi Kinugasa-Katayama, Youngseok Lee, Nam Hee Won, Elizabeth S. Nakasone, Stephen A. Hearn, Victoria Küttner, Jing Qiu, Ana S. Almeida, Naiara Perurena, Kai Kessenbrock, Michael S. Goldberg, Mikala Egeblad

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170 Citations (Scopus)

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 metastasispromoting tumor-host interaction and a potential therapeutic target. 2016

Original languageEnglish
Article number361ra138
JournalScience Translational Medicine
Volume8
Issue number361
DOIs
Publication statusPublished - 2016 Oct 19

ASJC Scopus subject areas

  • Medicine(all)

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    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., Küttner, V., Qiu, J., Almeida, A. S., Perurena, N., Kessenbrock, K., Goldberg, M. S., & Egeblad, M. (2016). Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Science Translational Medicine, 8(361), [361ra138]. https://doi.org/10.1126/scitranslmed.aag1711