Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells
Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells
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DOI：
10.1016/j.devcel.2018.02.015
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发表时间：
2018-04-09
影响因子：
11.8
通讯作者：
Goetz, Jacky G.
中科院分区：
文献类型：
--
作者：
Follain, Gautier;Osmani, Nael;Goetz, Jacky G.
转移播种是由细胞内在和环境线索驱动的，但生物力学的贡献知之甚少。我们的目的是阐明血流对体内循环肿瘤细胞（CTC）的阻滞和外渗的影响。使用斑马鱼胚胎，我们表明，逮捕的CTC发生在血管中具有良好的流动配置文件，其中流动力控制的CTC内皮细胞的粘附功效。我们通过生物药理学鉴定了允许成功阻止CTC的流动和粘附力的阈值。此外，流动力通过损害内皮的重塑特性来微调肿瘤细胞外渗。重要的是，我们还观察到在小鼠脑毛细血管中CTC的停滞位点处的内皮重塑。最后，我们观察到人幕上脑转移瘤最好发生在低灌注区。这些结果表明，在转移部位的血流动力学曲线调节转移性生长之前的外渗的关键步骤。
Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium. We biophysically identified the threshold values of flow and adhesion forces allowing successful arrest of CTCs. In addition, flow forces fine-tune tumor cell extravasation by impairing the remodeling properties of the endothelium. Importantly, we also observe endothelial remodeling at arrest sites of CTCs in mouse brain capillaries. Finally, we observed that human supratentorial brain metastases preferably develop in areas with low perfusion. These results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth.