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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Chemokines, cytokines and exosomes help tumors to shape inflammatory microenvironment.
Kamar-Sulu N. Atretkhany,M. S. Drutskaya,Sergei A. Nedospasov,Sergei I. Grivennikov,Sergei I. Grivennikov,Dmitry V. Kuprash,Dmitry V. Kuprash +6 more
TL;DR: The contributions of chemokines, cytokines and exosomes to the processes such as induction of inflammation and tumorigenesis are discussed, concluding that tumor-elicited inflammation is a key driver of tumor progression and an essential component of tumor microenvironment.
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Never Travel Alone: The Crosstalk of Circulating Tumor Cells and the Blood Microenvironment.
TL;DR: This review will discuss the recent research on the processes in the blood microenvironment with CTCs and will outline currently investigated treatment strategies.
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The regulation of pre-metastatic niche formation by neutrophils
TL;DR: An up to date overview of the different roles neutrophils play in regulating the metastatic processes is provided.
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Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus
Elmar Pieterse,Julia M. Hofstra,Jo H. M. Berden,Martin Herrmann,Jürgen Dieker,J. van der Vlag +5 more
TL;DR: Treatment of neutrophils with histone deacetylase (HDAC) inhibitor Trichostatin A, prior to induction of NETosis, induced NETs containing hyperacetylated histones, endowed with an increased capacity to activate macrophages, implying that specific histone modifications, in particular acetylation, might enhance the immunostimulatory potential of NETs in SLE.
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Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease.
TL;DR: Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli.
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