Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis.
Pancreatic Cancer-Induced Neutrophil Extracellular Traps: A Potential Contributor to Cancer-Associated Thrombosis.
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DOI：
10.3390/ijms18030487
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发表时间：
2017-02-24
影响因子：
5.6
通讯作者：
Metharom P
中科院分区：
文献类型：
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作者：
Abdol Razak N;Elaskalani O;Metharom P
胰腺癌（PaCa）是一种高度转移的癌症，患者发生静脉血栓栓塞（VTE）的风险很高。中性粒细胞胞外陷阱（NET）与癌症转移和癌症相关血栓形成有关，但癌症刺激NET释放的能力尚不清楚。NETs的释放是一个缓慢的过程，需要活性氧（ROS）的产生。研究表明，活化的血小板是释放的重要介质。在这里，我们发现PaCa细胞可以刺激NETs的快速释放，而不依赖于ROS的产生。我们进一步评估了血小板在paca诱导的NETs中的作用，并观察到paca引发的血小板增加NET释放的趋势。此外，NETs促进体外静脉剪切应力下血栓的形成。综上所述，我们的研究结果表明，PaCa诱导的NETs可能导致PaCa患者发生静脉血栓栓塞的高风险，并表明NETs是一种潜在的治疗靶点。
Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production. We further assessed the role of platelets in PaCa-induced NETs and observed a trend of increased the NET release by PaCa-primed platelets. Additionally, NETs promoted thrombus formation under venous shear stress ex vivo. Taken together, our results suggest that PaCa-induced NETs can contribute to the high risk of venous thromboembolism development in PaCa patients, and reveal NETs as a potential therapeutic target.