Evidence and impact of neutrophil extracellular traps in malignant melanoma

Schedel, Fiona; Mayer‐Hain, Sarah; Pappelbaum, Karin I.; Metze, Dieter; Stöck, Martin; Goerge, Tobias; Loser, Karin; Sunderkötter, Cord; Luger, Thomas A.; Weishaupt, Carsten

doi:10.1111/pcmr.12818

Cited by 64 publications

(41 citation statements)

References 32 publications

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“…NETs can exert an anti-tumor or pro-tumor activity. NET components like myeloperoxidase (MPO) ( 21 ), proteinases ( 20 , 22 ), and histones ( 23 ) can kill a tumor, inhibit tumor growth, and metastasis ( 21 ). NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation, and metastasis ( 20 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis

et al. 2020

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Neutrophil Extracellular Traps (NETs) are net-like structures composed of DNA-histone complexes and proteins released by activated neutrophils. In addition to their key role in the neutrophil innate immune response, NETs are also involved in autoimmune diseases, like systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and in other non-infectious pathological processes, as coagulation disorders, thrombosis, diabetes, atherosclerosis, vasculitis, and cancer. Recently, a large body of evidence indicates that NETs are involved in cancer progression and metastatic dissemination, both in animal models and cancer patients. Interestingly, a close correlation between cancer cell recruitment of neutrophils in the tumor microenvironment (Tumor Associated Neutrophils. TANs) and NET formation has been also observed either in primary tumors and metastatic sites. Moreover, NETs can also catch circulating cancer cells and promote metastasis. Furthermore, it has been reported that wake dormant cancer cells, causing tumor relapse and metastasis. This review will primarily focus on the pro-tumorigenic activity of NETs in tumors highlighting their ability to serve as a potential target for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis

et al. 2020

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“…Because of the positive relationship between the dosage of LPS and NETosis, such a result indicates the cytotoxicity effect of NETosis on tumor cells. It has been reported that NETs can exhibit an anti-tumor effect through the high local concentration of granule-derived positive proteins released in the NETosis Cell Reports 33, 108499, December 15, 2020 3 Article ll process (Arelaki et al, 2016;Schedel et al, 2020). The apoptosis assay, using by flow cytometry, and the viability/ cytotoxicity assay, using staining by live/dead cell imaging kit, also had results similar to the CCK8 assay.…”

Section: Photo-activated Ros Generation and Enhanced Tumor Killing Activity Of Ne P Smentioning

confidence: 79%

Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy

Han

et al. 2020

Cell Reports

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“…Despite that there are a number of studies about NETs, it is difficult to prove whether NETs have a pro-tumor effect or an anti-tumor effect. However, in the data that present the anti-tumor effect of NETs, like in Fiona Schedel's study (24), the researcher added NETs other than with neutrophils into the cell culture media. It may be the components of NETs that play an anti-tumor role.…”

Section: Discussionmentioning

confidence: 99%

“…Not only histones provide a site for the pathogen to bind, but the DNA structure also plays an important role in capturing cancer cells. The study we mentioned above (24) found that when melanoma cell line A375 was co-cultured with NETs, their ability to metastasize and proliferate declined. In vivo experiment showed the same result.…”

Section: Anti-tumor Effect Of Netsmentioning

confidence: 94%

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The pro-tumor effect and the anti-tumor effect of neutrophils extracellular traps

Liu

2019

BST

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For decades, neutrophils were considered to be a significant infection defender for both innate and acquired immune systems. It was understood that neutrophils act in two ways: either by releasing antimicrobial proteins through degranulation into extracellular space or by phagocytosis of pathogenic microbes. However, a series of recent findings suggest that neutrophils could play their roles in another way: neutrophils extracellular traps (NETs) (1). NETs were first found in 2004 (2). When neutrophils are activated, they can form extracellular fibrous structures composed of DNA and some proteins from azurophilic, specific and tertiary granules derived from activated neutrophils. Among these components, histones comprise the highest proportion of NETs (3). The remainder of proteins that exist on the DNA scaffold include granular protein, cytoplasmic proteins, cytoskeletal proteins, and some other enzymes. Most of these molecules have been shown to participate in both direct and indirect pathogen-killing mechanisms. With such a number of proteins, as a result, NETs can influence the internal environment in different ways (4). Although NETs play an important role in killing pathogenic microbes like bacteria or fungi, in some conditions when it is excessively generated, NETs can do harm to the human body (5). For instance, evidence showed that is can promote vasculitis and thrombosis. Moreover, NETs have been implicated in sterile inflammation diseases such as rheumatoid arthritis and systematic lupus erythematosus (6). Recently, some studies have found that NETs are also involved with tumors. Nevertheless, these results go in two different directions: one is NETs can promote tumor proliferation, invasion, and metastasis, while the other suggests that NETs can inhibit cancer cell proliferation and invasion. Since this research was performed under different experimental conditions and the diseases being studied were different, there is not a clear conclusion on how NETs affect tumors or whether it is a pro-tumor factor or an anti-tumor factor. Summary Significant advances in our understanding of neutrophil biology were made in the past several years. A newly discovered mechanism was discovered, the formation of neutrophils extracellular traps (NETs). The structure of NETs is composed of the DNA strand and neutrophil granule proteins. NETs were found to have an association with tumor progression. This review highlights the latest knowledge about the controversial effect on tumors of NETs. Pro-tumor and anti-tumor effects are described respectively. The probable mechanisms of the anti-tumor effect are related to its direct killing of cancer cells or stimulation of the immune system to fight against the tumor. The pro-tumor effect has a correlation with matrix metalloproteinase 9 (MMP-9), cathepsin G, and neutrophil elastase (NE). Moreover, the structure of the NETs makes it able to catch the circulating tumor cells, which could lead to metastasis. This review summarizes our knowledge about the proven roles of NETs in th...

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Evidence and impact of neutrophil extracellular traps in malignant melanoma

Cited by 64 publications

References 32 publications

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis

Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy

The pro-tumor effect and the anti-tumor effect of neutrophils extracellular traps

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