Department of Chemical and Biomedical Engineering, West Virginia University, 1306 Evansdale Drive, ESB 521, Morgantown, WV, 26506, USA.
Department of Surgery, West Virginia University, Morgantown, WV, 26506, USA.
Breast Cancer Res. 2019 Dec 18;21(1):145. doi: 10.1186/s13058-019-1237-6.
The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer.
中性粒细胞胞外诱捕网（NETs）的形成，即 NETosis，最初被观察到是一种针对细菌感染的新型免疫反应，但此后在多种其他炎症性疾病状态中也发现了 NETosis 的异常发生，包括癌症。乳腺癌是女性中最常见的恶性肿瘤。在乳腺癌中，NETosis 与疾病进展、转移和并发症（如静脉血栓栓塞）的增加有关。针对 NET 的治疗方法在临床前癌症模型中取得了成功，并且可能成为减缓或阻止乳腺癌患者肿瘤进展的有价值的临床靶点。我们将简要概述 NETs 可能在肿瘤微环境和循环中形成的机制，包括中性粒细胞、肿瘤细胞、内皮细胞和血小板之间的串扰，以及癌症相关细胞外囊泡在调节中性粒细胞行为和 NET 挤出中的作用。我们还将探讨癌症相关 NETosis 的预后意义，并开发旨在靶向 NET 相互作用的新型治疗方法，以改善乳腺癌患者的预后。
