Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Jonathan Cools-Lartigue,Jonathan Spicer,Braedon McDonald,Stephen Gowing,Simon C. Chow,Betty Giannias,Paul Kubes,Lorenzo E. Ferri +7 more
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TLDR
It is reported that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions and NETs are identified as potential therapeutic targets in the context of systemic infection.Abstract:
The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.read more
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Journal ArticleDOI
Neutrophils and Granulocytic MDSC: The Janus God of Cancer Immunotherapy.
Serena Zilio,Paolo Serafini +1 more
TL;DR: Understanding the biology of these cells and influencing their polarization in the tumor micro- and macro-environment may be the key for the development of new therapeutic strategies, which may finally hold the promise of an effective immunotherapy for cancer.
Journal ArticleDOI
Infiltrating Myeloid Cells Exert Protumorigenic Actions via Neutrophil Elastase
Irina Lerman,Maria de la Luz Garcia-Hernandez,Javier Rangel-Moreno,Luis Chiriboga,Chunliu Pan,Kent L. Nastiuk,John J. Krolewski,Aritro Sen,Stephen R. Hammes +8 more
TL;DR: It was determined that NE is expressed by infiltrating immune cells and is enzymatically active in prostate cancer xenografts and in prostate tumors of prostate-specific Pten-null mice, suggesting that MDSCs and NE are physiologically important mediators of prostate cancer progression and may serve as potential biomarkers and therapeutic targets.
Book ChapterDOI
Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease
TL;DR: The review highlights the current understanding of the role of ROS and RNS produced by neutrophils in health and disease and highlights the need to maintain the balance between ROS/RNS formation and removal.
Journal ArticleDOI
Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer.
Surashri Shinde-Jadhav,Surashri Shinde-Jadhav,Jose Joao Mansure,Roni F. Rayes,Roni F. Rayes,Gautier Marcq,Mina Ayoub,Mina Ayoub,Rodrigo Skowronski,Ronald Kool,Ronald Kool,Fadi Brimo,Jonathan Spicer,Jonathan Spicer,Wassim Kassouf,Wassim Kassouf +15 more
TL;DR: In this article, a role for neutrophil extracellular traps (NETs) as players in tumor radioresistance was demonstrated using a syngeneic bladder cancer model.
Journal ArticleDOI
Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis
M. Inoue,Ryota Nakashima,Masahiro Enomoto,Yuhki Koike,Xiao Zhao,Kenneth W. Yip,Shao Hui Huang,John Waldron,John Waldron,Mitsuhiko Ikura,Mitsuhiko Ikura,Fei-Fei Liu,Scott V. Bratman +12 more
TL;DR: Plasma redox imbalance caused by albumin oxidation is shown to induce inflammation-independent NETosis and lung metastasis, andalbumin oxidation and reduced plasma free thiol to be associated with pulmonary metastasis in a cohort of head and neck cancer patients.
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