Circulating endothelial cells in cancer patients do not express tissue factor
Circulating endothelial cells in cancer patients do not express tissue factor
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DOI：
10.1016/j.canlet.2004.04.019
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发表时间：
2004-09-30
期刊：
影响因子：
9.7
通讯作者：
Voest, EE
中科院分区：
文献类型：
--
作者：
Beerepoot, LV;Mehra, N;Voest, EE
循环内皮细胞（CEC）的数量在具有进行性疾病的癌症患者中增加。此外，癌症患者发生血栓形成事件的风险增加，与预后呈负相关。组织因子（TF）是凝血的生理起始因子，存在于许多血管外细胞的表面。在来自癌症患者的34个样本和来自志愿者的7个样本中，对CEC进行定量（使用内皮特异性抗CD 146珠），并使用显色测定法评估TF活性。所有样品显示非常有限的TF活性（患者：1.6 +/- 3.1 μ U;志愿者：0.94 1 +/- 1.7 μ U FXa/100 CEC，通过Mann-Whitney检验P = 0.30）。在体外TNF α刺激后，来自癌症患者和志愿者的CEC均显示出显著增加的TF活性（内源性活性：17.3 +/-6.4 muU; TNF α刺激后：73.8 +/-34.3 muU FXa; P = 0.028，Wilcoxon符号秩检验），反映了CEC产生生物活性TF的潜力。由于显色试验确定了平均细胞TF活性，我们还分析了免疫组织化学TF抗原表达CEC子集。TF-抗原表达不可检测。从癌症患者分离的CEC不表达TF。CEC在刺激后可以产生功能性TF，因此可能在（肿瘤内）凝血诱导和肿瘤血管生成中发挥作用。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Numbers of circulating endothelial cells (CECs) are increased in cancer patients with progressive disease. Also, cancer patients have an increased risk for thrombotic events, being negatively associated with prognosis. Tissue factor (TF), the physiological initiator of coagulation, is present on the surface of many extravascular cells. In 34 samples from cancer patients and in seven from volunteers, CECs were quantified (with endothelium-specific anti-CD146 beads), and TF-activity assessed with a chromogenic assay. All samples displayed very limited TF-activity (patients: 1.6 +/- 3.1 muU; volunteers: 0.94 1 +/- 1.7 muU FXa/100 CECs, P = 0.30 by Mann-Whitney test). After in vitro TNFalpha-stimulation, CECs from both cancer patients and volunteers showed substantially increased TF-activity (endogenous activity: 17.3 +/- 6.4 muU; after TNFalpha-stimulation: 73.8 +/- 34.3 muU FXa; P = 0.028, Wilcoxon signed ranks test), reflecting the potential of CECs to generate biologically active TF. As the chromogenic assay determines a mean cellular TF-activity, we also analyzed immunohistochemical TF-antigen expression on CEC subsets. TF-antigen expression was undetectable. CECs isolated from cancer patients do not express TF. CECs can generate functional TF after stimulation and may therefore play a role in (intratumoral) coagulation induction and tumor angiogenesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.