Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study.
Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study.
复制标题
DOI：
10.1371/journal.pone.0159170
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Moon GJ
中科院分区：
文献类型：
--
作者：
Bang OY;Chung JW;Lee MJ;Kim SJ;Cho YH;Kim GM;Chung CS;Lee KH;Ahn MJ;Moon GJ
众所周知，癌症和中风是老年人最常见的死亡原因。然而，导致癌症患者中风的病理机制尚不清楚。循环细胞外囊泡（EV）在癌症相关血栓形成和肿瘤进展中发挥作用。因此，我们假设癌细胞衍生的EV引起癌症相关的凝血病，导致缺血性卒中。D-二聚体和表达癌细胞标志物的EV的血清水平（上皮细胞粘附分子[CD 326]），组织因子（TF [CD 142]），内皮细胞采用流式细胞术检测了155例缺血性卒中和活动性癌症患者的血小板（CD 31 + CD 42 b-）和血小板（CD 62 P）（116例-癌症相关，39例-传统卒中机制），（B）25例缺血性卒中患者（无癌症），（c）32例无卒中的癌症患者，以及（d）101例健康受试者。癌细胞源性EV水平与D-二聚体和TF+ EV水平相关。癌性脑卒中患者癌细胞源性EVs（CD 326+和CD 326 + CD 142+）水平高于其他各组（P<0.05）。通径分析表明，癌细胞源性EV通过D-二聚体水平测量的凝血障碍与卒中相关。TF+ EV和D-二聚体之间的相关性较差，通径分析表明，癌细胞来源的EV可能导致癌症相关的凝血功能障碍，而与TF+ EV的水平无关。我们的研究结果表明，癌细胞衍生的EV介导凝血功能障碍，通过TF非依赖性机制导致缺血性卒中。
Cancer and stroke, which are known to be associated with one another, are the most common causes of death in the elderly. However, the pathomechanisms that lead to stroke in cancer patients are not well known. Circulating extracellular vesicles (EVs) play a role in cancer-associated thrombosis and tumor progression. Therefore, we hypothesized that cancer cell-derived EVs cause cancer-related coagulopathy resulting in ischemic stroke. Serum levels of D-dimer and EVs expressing markers for cancer cells (epithelial cell adhesion molecule [CD326]), tissue factor (TF [CD142]), endothelial cells (CD31+CD42b-), and platelets (CD62P) were measured using flow cytometry in (a) 155 patients with ischemic stroke and active cancer (116 − cancer-related, 39 − conventional stroke mechanisms), (b) 25 patients with ischemic stroke without cancer, (c) 32 cancer patients without stroke, and (d) 101 healthy subjects. The levels of cancer cell-derived EVs correlated with the levels of D-dimer and TF+ EVs. The levels of cancer cell-derived EVs (CD326+ and CD326+CD142+) were higher in cancer-related stroke than in other groups (P<0.05 in all the cases). Path analysis showed that cancer cell-derived EVs are related to stroke via coagulopathy as measured by D-dimer levels. Poor correlation was observed between TF+ EV and D-dimer, and path analysis demonstrated that cancer cell-derived EVs may cause cancer-related coagulopathy independent of the levels of TF+ EVs. Our findings suggest that cancer cell-derived EVs mediate coagulopathy resulting in ischemic stroke via TF-independent mechanisms.