Development of coagulation factor probes for the identification of procoagulant circulating tumor cells.
Development of coagulation factor probes for the identification of procoagulant circulating tumor cells.
复制标题
DOI：
10.3389/fonc.2012.00110
复制
发表时间：
2012
影响因子：
4.7
通讯作者：
McCarty OJ
中科院分区：
文献类型：
--
作者：
Tormoen GW;Cianchetti FA;Bock PE;McCarty OJ
转移性癌症与高凝状态相关，病理性静脉血栓栓塞性疾病是癌症患者发病率的重要来源和第二大死亡原因。在这里，我们旨在开发一种新的标记策略，以检测和定量来自转移性癌症患者的促凝血循环肿瘤细胞（CTC）。我们假设促凝血CTC的计数可能是癌症患者静脉血栓形成的预后指标。我们的方法是基于这样的观察，即癌细胞能够在体外启动和促进细胞介导的凝血，从而激活凝血因子复合物组装在癌细胞膜表面上。在纯化系统、抗凝血液和血浆以及凝血条件下的血浆中，对荧光标记的活性位点抑制的凝血因子VIIa、Xa和IIa与转移性乳腺癌细胞系MDA-MB-231、非转移性结肠直肠细胞系SW 480或转移性结肠直肠细胞系SW 620的结合进行了表征。我们的结论是，CTC标记策略，利用基于凝血因子的荧光探针可以提供一个功能评估的促凝潜力的CTC，这种策略是适合目前的CTC检测平台。
Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.