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靶向中性粒细胞胞外诱捕网在癌症进展与转移中的作用

Targeting neutrophil extracellular traps in cancer progression and metastasis

作者:Ji Zhang, Changhong Miao, Hao Zhang

期刊:Theranostics

摘要

中性粒细胞作为免疫系统的重要效应器和调节因子,其作用不可或缺,涵盖了病原体的清除以及在癌症的发生和发展中的关键角色。相反,恶性肿瘤对中性粒细胞的活性、成熟和寿命也具有深远影响。癌细胞通过操控其生物学特性以增强或抑制中性粒细胞的关键功能。这种调控机制是中性粒细胞最为显著的防御机制之一,包括形成中性粒细胞胞外诱捕网(NETs)。NETs由DNA、组蛋白和细胞毒性颗粒蛋白组成的纤维状结构。在本文中,我们讨论了癌症诱导NET形成及其在促进癌症进展中的双向作用,特别关注中性粒细胞和NETs引起的血管功能障碍及血栓形成如何增加癌症患者心血管并发症的死亡风险。最后,提出了一系列具有潜力的治疗策略,以期在临床中有效靶向NETs。

Abstract

Neutrophils serve as pivotal effectors and regulators of the intricate immune system. Their contributions are indispensable, encompassing the obliteration of pathogens and a significant role in both cancer initiation and progression. Conversely, malignancies profoundly affect neutrophil activity, maturation, and lifespans. Cancer cells manipulate their biology to enhance or suppress the key functions of neutrophils. This manipulation is one of the most remarkable defensive mechanisms used by neutrophils, including the formation of neutrophil extracellular traps (NETs). NETs are filamentous structures comprising DNA, histones, and proteins derived from cytotoxic granules. In this review, we discuss the bidirectional interplay in which cancer elicits NET formation, and NETs concurrently facilitate cancer progression. Here, we discuss how vascular dysfunction and thrombosis induced by neutrophils and NETs contribute to an elevated risk of mortality from cardiovascular complications in patients with cancer. Ultimately, we propose a series of therapeutic strategies that hold promise for effectively targeting NETs in clinical settings.

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