Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps
| Autor: | Victoria Küttner, Youngseok Lee, Michael S. Goldberg, Yumi Kinugasa-Katayama, Kai Kessenbrock, Stephen Hearn, Juwon Park, Nam Hee Won, Zohreh Amoozgar, Julie M. Jorns, Naiara Perurena, Laura Maiorino, Mikala Egeblad, Jing Qiu, Elizabeth S. Nakasone, Ana S. Almeida, Robert W. Wysocki, Anne F. Schott, Miriam R. Fein |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Extracellular Traps Lung Neoplasms Neutrophils Triple Negative Breast Neoplasms Biology Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Animals Deoxyribonuclease I Humans Neoplasm Metastasis Lung Mice Inbred BALB C Proteolytic enzymes Cancer General Medicine Neutrophil extracellular traps medicine.disease Molecular biology Metastatic breast cancer 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Nanoparticles |
| Zdroj: | Science Translational Medicine. 8 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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