Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis.
Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis.
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DOI：
10.3390/cancers13174495
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发表时间：
2021-09-06
期刊：
影响因子：
5.2
通讯作者：
Demkow U
中科院分区：
文献类型：
--
作者：
Demkow U
本文就中性粒细胞胞外陷阱（NETs）的致瘤作用作一综述。在各种人类和动物肿瘤样本中发现了NETs。NETs在肿瘤发展中的作用越来越多地包括癌症免疫编辑和免疫系统与癌细胞之间的相互作用。net唤醒处于休眠状态的癌细胞，在肿瘤微环境中发挥关键的调节作用，并通过增强肿瘤的迁移和侵袭能力来加剧肿瘤的侵袭性。此外，NETs还能诱导肿瘤细胞从上皮细胞向间质细胞转变。NET蛋白酶还能降解细胞外基质，促进癌细胞外渗。此外，NETs可以捕获循环癌细胞，从而促进转移。更好地了解癌症和net之间的相互作用可以帮助设计新的治疗干预方法，阻断癌症逃避机制并防止转移性扩散。目前的综述强调了癌症和中性粒细胞胞外陷阱（NETs）之间复杂的相互作用。中性粒细胞是抵御外来入侵者的第一道防线，主要的效应机制包括：吞噬、脱颗粒和net的形成。NETs由去致密核或线粒体DNA组成，并装饰有蛋白酶和各种炎症介质。尽管NETs在防御全身性感染方面起着至关重要的作用，但它们也参与非传染性疾病，如炎症、自身免疫性疾病和癌症。癌细胞招募中性粒细胞（肿瘤相关中性粒细胞，TANs），向肿瘤微环境释放NETs。NETs存在于各种人类和动物肿瘤样本中，如胰腺癌、乳腺癌、肝癌和胃癌以及转移性肿瘤周围。NETs在肿瘤发展中的作用越来越多地包括癌症免疫编辑和免疫系统与癌细胞之间的相互作用。根据积累的证据，net唤醒了处于休眠状态的癌细胞，导致肿瘤复发，并无限制地生长和扩散。NETs在肿瘤微环境中发挥着关键的调节作用，例如通过蛋白酶（即基质金属蛋白酶和促炎细胞因子）的分泌，促进远处转移的发生。此外，net通过增强肿瘤的迁移和侵袭能力，直接加剧了肿瘤的侵袭性。收集到的证据还表明，通过诱导高迁移率组框1，NETs诱导肿瘤细胞上皮向间质转化，从而增强其侵袭性。NET蛋白酶还能降解细胞外基质，促进癌细胞外渗。此外，NETs可以捕获循环癌细胞，从而促进转移。net通过其蛋白酶或激活信号直接触发肿瘤细胞增殖。这篇综述的重点是NETs的促肿瘤作用，尽管它也可能表现出抗肿瘤作用。NET成分，如髓过氧化物酶或组蛋白，已被证明可以直接杀死癌细胞。更好地了解癌症和net之间的相互作用可以帮助设计新的治疗干预方法，阻断癌症逃避机制并防止转移性扩散。本综述旨在提供有关net与癌症之间的串扰的最新知识，并为未来探索这一领域的科学家带来更深刻的想法。
This review focuses on the pro-tumorigenic action of neutrophil extracellular traps (NETs). NETs were found in various samples of human and animal tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between immune system and cancer cells. NETs awake dormant cancer cells, play a key regulatory role in the tumor microenvironment, and exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity. Furthermore, NETs induce the epithelial to mesenchymal transition in tumor cells. NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation. Moreover, NETs can entrap circulating cancer cells and, in that way, facilitate metastasis. A better understanding of the crosstalk between cancer and NETs can help to devise novel approaches to the therapeutic interventions that block cancer evasion mechanisms and prevent metastatic spread. The present review highlights the complex interactions between cancer and neutrophil extracellular traps (NETs). Neutrophils constitute the first line of defense against foreign invaders using major effector mechanisms: phagocytosis, degranulation, and NETs formation. NETs are composed from decondensed nuclear or mitochondrial DNA decorated with proteases and various inflammatory mediators. Although NETs play a crucial role in defense against systemic infections, they also participate in non-infectious conditions, such as inflammation, autoimmune disorders, and cancer. Cancer cells recruit neutrophils (tumor-associated neutrophils, TANs), releasing NETs to the tumor microenvironment. NETs were found in various samples of human and animal tumors, such as pancreatic, breast, liver, and gastric cancers and around metastatic tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between the immune system and cancer cells. According to the accumulated evidence, NETs awake dormant cancer cells, causing tumor relapse, as well as its unconstrained growth and spread. NETs play a key regulatory role in the tumor microenvironment, such as the development of distant metastases through the secretion of proteases, i.e., matrix metalloproteinases and proinflammatory cytokines. NETs, furthermore, directly exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity. The collected evidence also states that through the induction of the high-mobility group box 1, NETs induce the epithelial to mesenchymal transition in tumor cells and, thereby, potentiate their invasiveness. NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation. Moreover, NETs can entrap circulating cancer cells and, in that way, facilitate metastasis. NETs directly trigger tumor cell proliferation through their proteases or activating signals. This review focused on the pro-tumorigenic action of NETs, in spite of its potential to also exhibit an antitumor effect. NET components, such as myeloperoxidase or histones, have been shown to directly kill cancer cells. A better understanding of the crosstalk between cancer and NETs can help to devise novel approaches to the therapeutic interventions that block cancer evasion mechanisms and prevent metastatic spread. This review sought to provide the most recent knowledge on the crosstalk between NETs and cancer, and bring more profound ideas for future scientists exploring this field.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
4.6
作者：
Das A;Monteiro M;Barai A;Kumar S;Sen S
通讯作者：
Sen S
DOI：
10.1016/j.jaccao.2021.03.001
发表时间：
2021-06
期刊：
JACC. CardioOncology
影响因子：
--
作者：
Gervaso L;Dave H;Khorana AA
通讯作者：
Khorana AA
术后腹腔中的低密度中性粒细胞（LDN）通过产生中性粒细胞胞外捕获物（NET）来帮助腹膜复发。
影响因子：
4.6
作者：
Kanamaru R;Ohzawa H;Miyato H;Matsumoto S;Haruta H;Kurashina K;Saito S;Hosoya Y;Yamaguchi H;Yamashita H;Seto Y;Lefor AK;Sata N;Kitayama J
通讯作者：
Kitayama J
影响因子：
7.3
作者：
Berger-Achituv S;Brinkmann V;Abed UA;Kühn LI;Ben-Ezra J;Elhasid R;Zychlinsky A
通讯作者：
Zychlinsky A