结直肠癌中性粒细胞胞外诱捕网研究进展
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1.中国人民解放军联勤保障部队第九四〇医院 消化内科,甘肃 兰州 730050;2.甘肃中医药大学第一临床医学院, 甘肃 兰州 730000

作者简介:

贾栋,甘肃中医药大学第一临床医学院硕士研究生,主要从事消化道肿瘤的基础和临床方面的研究。

基金项目:

甘肃省自然科学基金资助项目(22JR11RA009);甘肃省科技厅科技计划基金资助项目(20JR10RA017);甘肃省兰州市人才创新基金资助项目(2020-RC-111)。


Research progress on neutrophil extracellular traps in colorectal cancer
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1.Department of Gastroenterology, 940th Hospital, PLA Joint Logistic Support Force, Lanzhou 730050, China;2.the First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730000, China

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    摘要:

    中性粒细胞胞外诱捕网(NETs)是中性粒细胞在病毒、细菌、免疫复合物、细胞因子等各种刺激作用下释放到胞外的由DNA染色质和多种颗粒蛋白构成的特殊网状物。作为先天性免疫胞外防御体系的重要组成部分,在正常情况下,NETs可介导抗菌活性并清除病原体,维持机体免受外界侵害,而过量或功能失调的NETs可进一步扩大炎症反应,并推动多类疾病的发生发展。NETs形成与自身免疫病、糖尿病、心血管疾病、癌症等发生发展密切相关。笔者就NETs形成在调控结直肠癌(CRC)发生发展中的作用进行综述,探讨NETs形成促进CRC的增殖、上皮-间质转化、血管生成、免疫逃避及肿瘤相关的血栓形成等恶性生物学行为的机制,并探讨NETs形成作为CRC生物标志物及潜在治疗靶点的临床应用前景。

    Abstract:

    Neutrophil extracellular traps (NETs) are special networks composed of DNA chromatin and various granular proteins that neutrophils release extracellularly in response to stimuli such as viruses, bacteria, immune complexes, and cytokines. As an important component of the innate immune extracellular defense system, NETs play a crucial role. Under normal circumstances, NETs mediate antimicrobial activity and pathogen clearance, thereby maintaining the body's protection against external threats. However, excessive or dysfunctional NETs can further amplify inflammatory responses and contribute to the occurrence and development of various diseases. The formation of NETs is closely associated with autoimmune diseases, diabetes, cardiovascular diseases, cancer, and more. In this review, the authors provide an overview of the role of NETs formation in regulating the occurrence and development of colorectal cancer (CRC). The review discusses the mechanisms by which NETs formation promotes malignant biological behaviors in CRC, including proliferation, epithelial-mesenchymal transition, angiogenesis, immune evasion, and tumor-related thrombosis. Furthermore, the review discusses the clinical prospects of NETs formation as a biomarker and potential therapeutic target for CRC.

    图1 NETs形成及作用机制模式图 A:细胞溶解性NETs(当中性粒细胞受到PMA、IL-8等因素刺激后,通过活化NADPH氧化酶引起ROS释放,激活PAD4诱导组蛋白瓜氨酸化,导致染色体解聚;ROS的上调诱导胞浆内的NE和MPO从胞浆转运入核,切割组蛋白,导致染色质进一步解凝,最后核膜裂解,去解聚的染色质释放到细胞外);B:活体式NETs(中性粒细胞被病原体或DAMP激活后,与TLR2/4受体或补体受体相结合,不依赖于 NADPH氧化酶复合物,直接激活PAD4致使染色质解聚,过程中没有核膜及细胞膜的破坏,被包裹的染色质DNA以囊泡出芽的方式排出胞外)Fig.1 NETs formation and mechanisms A: Suicidal NETs (When neutrophils are stimulated by factors such as PMA, IL-8, they activate NADPH oxidase, leading to the release of ROS. This activation induces PAD4 to catalyze histone citrullination, resulting in chromatin decondensation. Elevated ROS levels facilitate the translocation of NE and MPO from the cytoplasm to the nucleus, where they cleave histones, leading to further decondensation of chromatin. Eventually, the nuclear membrane ruptures, releasing decondensed chromatin into the extracellular space); B: Vital NETs (Neutrophils, when activated by pathogens or DAMPs, bind to TLR2/4 receptors or complement receptors. This process does not rely on the NADPH oxidase complex and directly activates PAD4, leading to chromatin decondensation. No disruption of the nuclear or cell membrane occurs during this process. Encapsulated chromatin DNA is expelled from the cell through vesicle budding)
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贾栋,陈顺,解有成,康殷楠,赵宝银,仵朝晖,王俊科,于晓辉.结直肠癌中性粒细胞胞外诱捕网研究进展[J].中国普通外科杂志,2023,32(10):1599-1607.
DOI:10.7659/j. issn.1005-6947.2023.10.019

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  • 收稿日期:2022-11-22
  • 最后修改日期:2023-03-09
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  • 在线发布日期: 2023-11-02