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NETosis: A New Factor in Tumor Progression and Cancer-Associated Thrombosis

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TLDR
It is proposed that the rapid developments in the field of NETosis may provide new targets to combat the thrombotic consequences of cancer and perhaps even help to contain the disease itself.
Abstract
Neutrophils have long been known as innate immune cells that phagocytose and kill pathogens and mount inflammatory responses protecting the host from infection. In the past decades, new aspects of neutrophils have emerged unmasking their importance not only in inflammation but also in many pathological conditions including thrombosis and cancer. The 2004 discovery that neutrophils, upon strong activation, release decondensed chromatin to form neutrophil extracellular traps (NETs), has unveiled new avenues of research. Here, we review current knowledge regarding NETs in thrombosis, with a special focus on cancer-associated thrombosis as well as their potential role in cancer growth and metastasis. We discuss the prospective use of NET-specific biomarkers, such as citrullinated histone H3 and NET inhibitors, as tools to anticipate and fight cancer-associated thrombosis. We propose that the rapid developments in the field of NETosis may provide new targets to combat the thrombotic consequences of cancer and perhaps even help to contain the disease itself.

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Journal ArticleDOI

An emerging role for neutrophil extracellular traps in noninfectious disease

TL;DR: The role of NETosis in autoimmunity, coagulation, acute injuries and cancer, and whether extracellular DNA is always detrimental in sterile inflammation are described.
Journal ArticleDOI

Tumour-associated neutrophils in patients with cancer

TL;DR: The evidence correlating the neutrophil-to-lymphocyte ratio with prognosis is described, followed by a discussion on the predictive value of TANs, which remains debatable, with conflicting data from different cancer types.
Journal ArticleDOI

Life and death of circulating cell-free DNA.

TL;DR: Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management and the role of circulating DNA in pathophysiological processes is reviewed.
Journal ArticleDOI

Release of Neutrophil Extracellular Traps by Neutrophils Stimulated With Antiphospholipid Antibodies: A Newly Identified Mechanism of Thrombosis in the Antiphospholipid Syndrome

TL;DR: In this paper, the interaction of antiphospholipid antibodies (aPL) with neutrophils has been extensively studied to determine whether aPL activate neutrophil to release extracellular traps (NETs), thereby predisposing to the arterial and venous thrombosis inherent in the APS.
Journal ArticleDOI

New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation

TL;DR: The mechanisms of NETosis, its antimicrobial action, and role in autoimmune diseases, as well as the relatively new field of NET-associated mitochondrial DNA are discussed.
References
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Journal ArticleDOI

Neutrophil extracellular traps kill bacteria

TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
Journal ArticleDOI

Novel cell death program leads to neutrophil extracellular traps

TL;DR: This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.
Journal Article

DNA Fragments in the Blood Plasma of Cancer Patients: Quantitations and Evidence for Their Origin from Apoptotic and Necrotic Cells

TL;DR: By quantitative methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor gene, the fraction of plasma DNA derived from tumor cells is quantified and is consistent with the possibility that apoptotic and necrotic cells are a major source for plasma DNA in cancer patients.
Journal ArticleDOI

Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood

TL;DR: It is proposed that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis, where NETs have the greatest capacity for bacterial trapping.
Journal ArticleDOI

Extracellular DNA traps promote thrombosis

TL;DR: It is reported that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation and may further explain the epidemiological association of infection with thrombosis.
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