The regulatory mechanism of neutrophil extracellular traps in cancer biological behavior

Abstract

As the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.

Increased blood neutrophil extracellular traps (NETs) associated with early life stress: translational findings in recent-onset schizophrenia and rodent model

“…NETs have also been involved in brain disorders, including stroke, traumatic brain injury, multiple sclerosis, and Alzheimer’s disease [ 34 , 35 ]. Studies have been investigating anti-NETs compounds to treat or prevent clinical inflammatory diseases [ 27 , 29 , 32 , 36 , 37 ]. However, NETs have never been investigated in psychiatric disorders.…”

NETosis as an oncologic therapeutic target: a mini review

“…Simultaneously, hypercitrullination of histones is mediated by protein-arginine deiminase type 4 (PAD4), which is a nuclear enzyme that citrullinates arginine residues by converting the amine groups to ketones ( 12 ). PAD4 can also mediates chromatin decondensation, which is the defining feature of cellular rearrangement in the formation of the NET ( 13 ). This process is followed by actin cytoskeletal disassembly and extracellular release of decondensed DNA by exocytosis or during plasma membrane lysis (mediated by NE and the pore forming GASDERMIN D), depending on the type of NETosis ( 13 ).…”

“…PAD4 can also mediates chromatin decondensation, which is the defining feature of cellular rearrangement in the formation of the NET ( 13 ). This process is followed by actin cytoskeletal disassembly and extracellular release of decondensed DNA by exocytosis or during plasma membrane lysis (mediated by NE and the pore forming GASDERMIN D), depending on the type of NETosis ( 13 ).…”

Neutrophil extracellular traps and complications of liver transplantation

“…Tumor metastasis is the main cause of cancer mortality, and neutrophils are involved in this process ( 139 ). Multiple studies reported that NETs trap circulating cancer cells and release proteases, which results in tumor metastasis and proliferation ( 35 , 140 ). Najmeh et al.…”