scholarly journals The Role of Neutrophil Extracellular Traps in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo-Zong Shao ◽  
Yi Yao ◽  
Jin-Ping Li ◽  
Ning-Li Chai ◽  
En-Qiang Linghu

Neutrophils are vital components of innate and adaptive immunity. It is widely acknowledged that in various pathological conditions, neutrophils are activated and release condensed DNA strands, triggering the formation of neutrophil extracellular traps (NETs). NETs have been shown to be effective in fighting against microbial infections and modulating the pathogenesis and progression of diseases, including malignant tumors. This review describes the current knowledge on the biological characteristics of NETs. Additionally, the mechanisms of NETs in cancer are discussed, including the involvement of signaling pathways and the crosstalk between other cancer-related mechanisms, including inflammasomes and autophagy. Finally, based on previous and current studies, the roles of NET formation and the potential therapeutic targets and strategies related to NETs in several well-studied types of cancers, including breast, lung, colorectal, pancreatic, blood, neurological, and cutaneous cancers, are separately reviewed and discussed.

2020 ◽  
Author(s):  
Sheniz Yuzeir ◽  
Liana Gercheva

It was recently proved that neutrophils and platelets are active participants in some inflammatory processes as well as a number of pathological conditions, including neoplastic diseases and thrombosis. It has been found that circulating neutrophils actively affect the mechanisms of tumour genesis, and along with platelets, act as independent regulators of different complications in infectious and malignant diseases. A few years ago, it was found that neutrophils have the ability to release extracellular traps (called neutrophil extracellular traps or NETs). Thus, neutrophils use both intracellular and extracellular mechanisms to limit inflammatory complications. Several recent studies confirmed that NETs increase considerably in malignant diseases, demonstrating that tumour-induced NETosis is a clinically significant process. It is recognised as an element of tumour biology, as it participates in tumour progression and angiogenesis. Neutrophils and the NETs released from them are stimulators of thrombotic processes in physiological and pathological conditions. Several reports demonstrate the connection between NETs and thrombosis. The presence of NETosis serves as a potential risk factor for thrombotic complications in malignant diseases. This chapter summarises the current knowledge of NETosis and the mechanisms that lead to the formation of NETs, including the role of circulating platelet–neutrophil complexes as regulators of tumour-induced NETosis in malignant diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1494 ◽  
Author(s):  
Antonio Magán-Fernández ◽  
Sarmad Muayad Rasheed Al-Bakri ◽  
Francisco O’Valle ◽  
Cristina Benavides-Reyes ◽  
Francisco Abadía-Molina ◽  
...  

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elcha Charles ◽  
Benjamin L. Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  

Abstract Background Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.


2021 ◽  
Author(s):  
Elcha Charles ◽  
Benjamin Dumont ◽  
Steven Bonneau ◽  
Paul-Eduard Neagoe ◽  
Louis Villeneuve ◽  
...  

Abstract Background: Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results: Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF w/o T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF without T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions: Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.


2018 ◽  
Vol 24 (6) ◽  
pp. 335-348 ◽  
Author(s):  
Carsten Deppermann ◽  
Paul Kubes

Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation. In this review we summarize the current knowledge about how platelets interact with the innate immune system during inflammation and infection and highlight recent advances in the field.


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