臨床上腫瘤患者經(jīng)常性出現(xiàn)癌癥相關(guān)的血栓，其發(fā)生的病理機(jī)制一直以來懸而未決,。
然而，可以明確的是血栓的出現(xiàn)與腫瘤患者的預(yù)后較差有密切聯(lián)系,，血栓是導(dǎo)致癌癥患者死亡的第二大原因,。
最近一項(xiàng)研究表明染色質(zhì)通過中性粒細(xì)胞形成的胞外菌網(wǎng)釋放到血液中是導(dǎo)致凝血和血栓的主要原因。研究人員使用慢性粒細(xì)胞性白血病小鼠模型發(fā)現(xiàn),，惡性和非惡性嗜中性粒細(xì)胞更容易形成胞外菌網(wǎng),。
這種胞外菌網(wǎng)的形成在乳腺癌和肺癌模型中也觀察到，這表明癌癥通過影響宿主系統(tǒng)誘發(fā)外周血中性粒細(xì)胞的增加,，導(dǎo)致胞外菌網(wǎng)更容易形成,。此外，在晚期乳腺癌模型中,，胞外菌網(wǎng)的形成伴隨肺靜脈血栓而出現(xiàn),。
在血栓前期階段給予癌癥老鼠模型低劑量LPS結(jié)合G-CSF后，發(fā)現(xiàn)血小板數(shù)目減少了,，微血栓形成也被抑制,。總之研究證實(shí)通過胞外菌網(wǎng)的形成所釋放的染色質(zhì)是導(dǎo)致癌癥患者血栓形成的主要原因之一,，或許這是一個(gè)在臨床上可以用來改善癌癥患者血栓癥狀的一個(gè)潛在靶標(biāo),。（生物谷：Bioon.com）
doi:10.1073/pnas.1200419109
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PMID:
Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis
Demers, M., D. S. Krause, et al.
Cancer-associated thrombosis often lacks a clear etiology. However, it is linked to a poor prognosis and represents the second-leading cause of death in cancer patients. Recent studies have shown that chromatin released into blood, through the generation of neutrophil extracellular traps (NETs), is procoagulant and prothrombotic. Using a murine model of chronic myelogenous leukemia, we show that malignant and nonmalignant neutrophils are more prone to NET formation. This increased sensitivity toward NET generation is also observed in mammary and lung carcinoma models, suggesting that cancers, through a systemic effect on the host, can induce an increase in peripheral blood neutrophils, which are predisposed to NET formation. In addition, in the late stages of the breast carcinoma model, NETosis occurs concomitant with the appearance of venous thrombi in the lung. Moreover, simulation of a minor systemic infection in tumor-bearing, but not control, mice results in the release of large quantities of chromatin and a prothrombotic state. The increase in neutrophil count and their priming is mediated by granulocyte colony-stimulating factor (G-CSF), which accumulates in the blood of tumor-bearing mice. The prothrombotic state in cancer can be reproduced by treating mice with G-CSF combined with low-dose LPS and leads to thrombocytopenia and microthrombosis. Taken together, our results identify extracellular chromatin released through NET formation as a cause for cancer-associated thrombosis and unveil a target in the effort to decrease the incidence of thrombosis in cancer patients.
