Clusters of circulating tumor cells traverse capillary-sized vessels
Clusters of circulating tumor cells traverse capillary-sized vessels
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DOI：
10.1073/pnas.1524448113
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发表时间：
2016-05-03
影响因子：
11.1
通讯作者：
Toner, Mehmet
中科院分区：
文献类型：
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作者：
Au, Sam H.;Storey, Brian D.;Toner, Mehmet
循环肿瘤细胞的多细胞聚集体（CTC 簇）是远处器官转移的有效引发剂。然而，目前认为 CTC 簇太大，无法通过狭窄的血管到达这些器官。在这里，我们通过使用微流体装置来挑战这一假设，该装置旨在模拟人体毛细血管收缩和从患者和癌细胞来源获得的 CTC 簇。即使在全血中，超过 90% 的包含多达 20 个细胞的细胞簇也能成功穿过 5 至 10 μm 的收缩区。簇快速且可逆地重组为单列链状几何形状，大大降低了它们的流体动力学阻力。将人类 CTC 簇异种移植到斑马鱼中，在体内表现出类似的重组和通过毛细血管大小的血管的转运。初步实验表明，在运输过程中，使用影响细胞相互作用能量的药物可能会破坏簇。这些发现表明，CTC 簇对肿瘤传播的作用可能比之前认为的更大，并可能为对抗 CTC 簇引发的转移提供策略。
Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-mu m constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis.