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 journalArticle

123 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

Fingerprint

Neoplasm Metastasis
Neoplasms
Neutrophils
Deoxyribonuclease I
Extracellular Traps
Triple Negative Breast Neoplasms
Breast Neoplasms
Lung
Infection
Nanoparticles
Leukocytes
Peptide Hydrolases
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Park, J., Wysocki, R. W., Amoozgar, Z., Maiorino, L., Fein, M. R., Jorns, J., ... 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

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

In: Science Translational Medicine, Vol. 8, No. 361, 361ra138, 19.10.2016.

Research output: Contribution to journalArticle

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
Park J, Wysocki RW, Amoozgar Z, Maiorino L, Fein MR, Jorns J et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Science Translational Medicine. 2016 Oct 19;8(361). 361ra138. https://doi.org/10.1126/scitranslmed.aag1711
Park, Juwon ; Wysocki, Robert W. ; Amoozgar, Zohreh ; Maiorino, Laura ; Fein, Miriam R. ; Jorns, Julie ; Schott, Anne F. ; Kinugasa-Katayama, Yumi ; Lee, Youngseok ; Won, Nam Hee ; Nakasone, Elizabeth S. ; Hearn, Stephen A. ; Küttner, Victoria ; Qiu, Jing ; Almeida, Ana S. ; Perurena, Naiara ; Kessenbrock, Kai ; Goldberg, Michael S. ; Egeblad, Mikala. / Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. In: Science Translational Medicine. 2016 ; Vol. 8, No. 361.
@article{b396a6edfbcf4c7692e12a0594562edb,
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. 2016",
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",
year = "2016",
month = "10",
day = "19",
doi = "10.1126/scitranslmed.aag1711",
language = "English",
volume = "8",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "361",

}

TY - JOUR

T1 - Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps

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

Y1 - 2016/10/19

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. 2016

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. 2016

UR - http://www.scopus.com/inward/record.url?scp=84991585703&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991585703&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aag1711

DO - 10.1126/scitranslmed.aag1711

M3 - Article

C2 - 27798263

AN - SCOPUS:84991585703

VL - 8

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 361

M1 - 361ra138

ER -