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 metastasis-promoting tumor-host interaction and a potential therapeutic target.
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Juwon
authors: J
authors: Park
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.|Medical Scientist Training Program, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.|Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Robert W
authors: RW
authors: Wysocki
authors: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors: Zohreh
authors: Z
authors: Amoozgar
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.|Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA.
authors: Laura
authors: L
authors: Maiorino
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.|Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
authors: Miriam R
authors: MR
authors: Fein
authors: University of Michigan, Ann Arbor, MI 48109, USA.
authors: Julie
authors: J
authors: Jorns
authors: University of Michigan, Ann Arbor, MI 48109, USA.
authors: Anne F
authors: AF
authors: Schott
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Yumi
authors: Y
authors: Kinugasa-Katayama
authors: Department of Pathology, Korea University Anam Hospital, Seoul, South Korea.
authors: Youngseok
authors: Y
authors: Lee
authors: Department of Pathology, Korea University Anam Hospital, Seoul, South Korea.
authors: Nam Hee
authors: NH
authors: Won
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.|Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA.
authors: Elizabeth S
authors: ES
authors: Nakasone
authors: Cold Spring Harbor Laboratory Cancer Center, NCI Shared Resources and St. Giles Foundation Advanced Microscopy Center, Cold Spring Harbor, NY 11724, USA.
authors: Stephen A
authors: SA
authors: Hearn
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Victoria
authors: V
authors: Küttner
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Jing
authors: J
authors: Qiu
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Ana S
authors: AS
authors: Almeida
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Naiara
authors: N
authors: Perurena
authors: University of California, Irvine, Irvine, CA 92697, USA.
authors: Kai
authors: K
authors: Kessenbrock
authors: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.|Department of Microbiology and Immunobiology at Harvard Medical School, Boston, MA 02115, USA.
authors: Michael S
authors: MS
authors: Goldberg
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. egeblad@cshl.edu.
authors: Mikala
authors: M
authors: Egeblad
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D003850:Deoxyribonuclease I / Q000737:chemistry; D065206:Extracellular Traps; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*
chemical_list: D003850:Deoxyribonuclease I