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

doi:10.1126/scitranslmed.aag1711

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

Research output: Contribution to journal › Article › peer-review

699 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.

Original language	English
Article number	361ra138
Journal	Science translational medicine
Volume	8
Issue number	361
DOIs	https://doi.org/10.1126/scitranslmed.aag1711
Publication status	Published - 2016 Oct 19
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Authors, some rights reserved;.

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/scitranslmed.aag1711

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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), Article 361ra138. https://doi.org/10.1126/scitranslmed.aag1711

Park, J, Wysocki, RW, Amoozgar, Z, Maiorino, L, Fein, MR, Jorns, J, Schott, AF, Kinugasa-Katayama, Y, Lee, Y, Won, NH, Nakasone, ES, Hearn, SA, Küttner, V, Qiu, J, Almeida, AS, Perurena, N, Kessenbrock, K, Goldberg, MS & Egeblad, M 2016, 'Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps', Science translational medicine, vol. 8, no. 361, 361ra138. https://doi.org/10.1126/scitranslmed.aag1711

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title = "Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps",

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.",

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

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AU - Park, Juwon

AU - Wysocki, Robert W.

AU - Amoozgar, Zohreh

AU - Maiorino, Laura

AU - Fein, Miriam R.

AU - Jorns, Julie

AU - Schott, Anne F.

AU - Kinugasa-Katayama, Yumi

AU - Lee, Youngseok

AU - Won, Nam Hee

AU - Nakasone, Elizabeth S.

AU - Hearn, Stephen A.

AU - Küttner, Victoria

AU - Qiu, Jing

AU - Almeida, Ana S.

AU - Perurena, Naiara

AU - Kessenbrock, Kai

AU - Goldberg, Michael S.

AU - Egeblad, Mikala

PY - 2016/10/19

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N2 - 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.

AB - 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.

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SN - 1946-6234

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Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

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