Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, 46026 Valencia, Spain.
Research Laboratory in Biomarkers in Reproduction, Gynaecology, and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain.
Int J Mol Sci. 2023 Mar 22;24(6):5995. doi: 10.3390/ijms24065995.
Neutrophils, the most abundant circulating leukocytes, play a well-known role in defense against pathogens through phagocytosis and degranulation. However, a new mechanism involving the release of neutrophil extracellular traps (NETs) composed of DNA, histones, calprotectin, myeloperoxidase, and elastase, among others, has been described. The so-called NETosis process can occur through three different mechanisms: suicidal, vital, and mitochondrial NETosis. Apart from their role in immune defense, neutrophils and NETs have been involved in physiopathological conditions, highlighting immunothrombosis and cancer. Notably, neutrophils can either promote or inhibit tumor growth in the tumor microenvironment depending on cytokine signaling and epigenetic modifications. Several neutrophils' pro-tumor strategies involving NETs have been documented, including pre-metastatic niche formation, increased survival, inhibition of the immune response, and resistance to oncologic therapies. In this review, we focus on ovarian cancer (OC), which remains the second most incidental but the most lethal gynecologic malignancy, partly due to the presence of metastasis, often omental, at diagnosis and the resistance to treatment. We deepen the state-of-the-art on the participation of NETs in OC metastasis establishment and progression and their involvement in resistance to chemo-, immuno-, and radiotherapies. Finally, we review the current literature on NETs in OC as diagnostic and/or prognostic markers, and their contribution to disease progression at early and advanced stages. The panoramic view provided in this article might pave the way for enhanced diagnostic and therapeutic strategies to improve the prognosis of cancer patients and, specifically, OC patients.
中性粒细胞是循环白细胞中最丰富的细胞，通过吞噬作用和脱颗粒作用在防御病原体方面发挥着众所周知的作用。然而，一种新的机制涉及到由 DNA、组蛋白、钙卫蛋白、髓过氧化物酶和弹性蛋白酶等组成的中性粒细胞细胞外陷阱 (NETs) 的释放，已经被描述。所谓的 NETosis 过程可以通过三种不同的机制发生：自杀、有活力和线粒体 NETosis。除了在免疫防御中的作用外，中性粒细胞和 NETs 还参与了生理病理条件，突出了免疫血栓形成和癌症。值得注意的是，中性粒细胞可以根据细胞因子信号和表观遗传修饰，在肿瘤微环境中促进或抑制肿瘤生长。已经记录了几种中性粒细胞促进肿瘤的策略，包括前转移生态位形成、增加存活、抑制免疫反应和对肿瘤治疗的耐药性。在这篇综述中，我们专注于卵巢癌 (OC)，它仍然是第二大偶发性但最致命的妇科恶性肿瘤，部分原因是转移的存在，通常在诊断时为网膜转移，以及对治疗的耐药性。我们深入探讨了 NETs 在 OC 转移建立和进展中的参与及其在化疗、免疫治疗和放射治疗耐药性中的作用。最后，我们综述了 NETs 在 OC 作为诊断和/或预后标志物的最新文献，以及它们在早期和晚期疾病进展中的作用。本文提供的全景视图可能为增强诊断和治疗策略铺平道路，以改善癌症患者的预后，特别是 OC 患者的预后。
