Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis
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DOI：
10.1172/jci67484
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发表时间：
2013-08-01
影响因子：
15.9
通讯作者：
Ferri, Lorenzo
中科院分区：
文献类型：
--
作者：
Cools-Lartigue, Jonathan;Spicer, Jonathan;Ferri, Lorenzo
大多数癌症患者至少接受一次手术作为治疗的一部分。严重的术后感染与不良的肿瘤学结局相关;然而，这种现象背后的机制尚不清楚。新出现的证据表明，中性粒细胞作为感染期间的第一道防线，促进了癌症的进展。神经细胞外陷阱（NET）是细胞外嗜中性粒细胞衍生的DNA网，响应于炎症信号释放，捕获并杀死入侵的病原体。NET在癌症进展中的作用完全未知。我们报告说，循环肿瘤细胞被困在NET在体外静态和动态条件下。在一个小鼠模型的感染盲肠结扎和穿刺，我们证明了微血管NET沉积和随后的陷阱循环肺癌细胞内的DNA网。NET捕获与肿瘤细胞注射后48小时的肝微转移形成增加和2周的总转移性疾病负荷增加相关。用DNA酶或中性粒细胞弹性蛋白酶抑制剂抑制NET可消除这些作用。这些发现暗示NET在全身感染的背景下在癌症转移的过程中，并确定NET作为潜在的治疗靶点。
The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.