最近，来自韩国圆光大学与美国哈佛大学医学院的研究小组合作发现，使用一种溶解血栓试剂抑制循环肿瘤细胞聚簇（circulating tumor cells clusters, CTC clusters）的形成可以有效延长转移型乳腺癌小鼠模型的生存期。相关研究结果发表在国际学术杂志Cancer Research上。

肿瘤病人血液中存在单个循环肿瘤细胞和循环肿瘤细胞聚簇，之前的研究发现循环肿瘤细胞聚簇的数量与肿瘤病人的生存期有一定相关性。循环肿瘤细胞聚簇比单个循环肿瘤细胞具有更强的转移性，可以作为肿瘤进展的预测因子。

在这项研究中，研究人员发现CTC clusters形成的相关特性。文章报道了早在原发性肿瘤组织临近血管中已能检测到循环肿瘤细胞聚簇，它在血液中的流动速度比单个循环肿瘤细胞慢，具有更强的转移灶形成能力。在血液循环中，单个循环肿瘤细胞与循环肿瘤细胞聚簇处于动态相互结合、解离过程。使用溶血栓试剂Urokinase溶解Fibrin能够抑制CTC clusters的形成，影响肿瘤细胞转移，延长肿瘤小鼠模型的生存期。

作者表示，光学成像观察能够帮助我们直接观察CTC clusters在血管中的动态变化过程。使用这种方法分析肿瘤病人的CTC聚簇对预测疾病进程有一些帮助。寻找干扰CTC clusters形成的药物可能为肿瘤治疗提供新的方法。

Urokinase Exerts Antimetastatic Effects by Dissociating Clusters of Circulating Tumor Cells

Choi JW, Kim JK, Yang YJ, Kim P, Yoon KH, Yun SH

  Clusters of circulating tumor cells (CTC) exhibit more robust metastatic properties than single CTC. Thus, understanding the distinct behaviors of CTC clusters and how CTC clustering is regulated may offer new insights into how to limit metastasis. In this study, we utilized an in vivo confocal system to observe the clustering behavior of CTC in real time, finding that the number of clusters increased proportionally with the growth of the primary tumor. Our experiments also indicated that the flow rate of the CTC clusters in blood vessels was relatively slower than single CTC due to increased vessel wall adhesion. Depending on disease stage, 5% to 10% of total CTC in circulation were in clusters, with this proportion increasing to >24% within lung metastases examined. Notably, in the 4T1 mouse model of breast cancer metastasis, we found that injecting host animals with urokinase-type plasminogen activator, a clinical thrombolytic agent, was effective at preventing the assembly of CTC clusters and prolonging overall host survival by approximately 20% relative to control animals. Our results suggest a tractable approach to limit metastasis by suppressing the formation or stability of CTC clusters circulating in the blood of cancer patients. Cancer Res; 75(21); 4474-82.