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Publication : Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps.

First Author  Park J Year  2016
Journal  Sci Transl Med Volume  8
Issue  361 Pages  361ra138
PubMed ID  27798263 Mgi Jnum  J:250211
Mgi Id  MGI:5923218 Doi  10.1126/scitranslmed.aag1711
Citation  Park J, et al. (2016) Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med 8(361):361ra138
abstractText  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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