A microfluidic model for organ-specific extravasation of circulating tumor cells.
A microfluidic model for organ-specific extravasation of circulating tumor cells.
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DOI：
10.1063/1.4868301
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发表时间：
2014-03
期刊：
影响因子：
3.2
通讯作者：
R. Riahi;Yongliang Yang;H. Kim;Linan Jiang;P. Wong;Y. Zohar
中科院分区：
文献类型：
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作者：
R. Riahi;Yongliang Yang;H. Kim;Linan Jiang;P. Wong;Y. Zohar
循环肿瘤细胞（ctc）是原发肿瘤非血液学癌症疾病扩散的主要载体，包括ctc外渗穿过血管壁，在远处器官形成继发性肿瘤。本文开发了一种基于聚二甲基硅氧烷的微流体系统，并对其进行了表征，用于体外系统研究ctc的器官特异性外渗。该系统概括了体内外渗微环境的两个主要方面：内皮单层血管中的局部信号趋化因子梯度。实验和数值研究了控制局部稳定趋化因子梯度、流速和初始趋化因子浓度的参数。实验还研究了微通道表面处理对施加剪切流的内皮单层的融合和粘附的影响。此外，还讨论了驱动ctc悬浮通过微流控系统的条件，同时维持局部趋化因子梯度和融合内皮单层。最后，利用微流控系统证明了CXCL12趋化因子梯度存在下MDA-MB-231癌细胞的外渗。与器官特异性外渗假说一致，对照实验证实了MDA-MB-231细胞迁移归因于趋化性而非随机过程的观察结果。
Circulating tumor cells (CTCs) are the principal vehicle for the spread of non-hematologic cancer disease from a primary tumor, involving extravasation of CTCs across blood vessel walls, to form secondary tumors in remote organs. Herein, a polydimethylsiloxane-based microfluidic system is developed and characterized for in vitro systematic studies of organ-specific extravasation of CTCs. The system recapitulates the two major aspects of the in vivo extravasation microenvironment: local signaling chemokine gradients in a vessel with an endothelial monolayer. The parameters controlling the locally stable chemokine gradients, flow rate, and initial chemokine concentration are investigated experimentally and numerically. The microchannel surface treatment effect on the confluency and adhesion of the endothelial monolayer under applied shear flow has also been characterized experimentally. Further, the conditions for driving a suspension of CTCs through the microfluidic system are discussed while simultaneously maintaining both the local chemokine gradients and the confluent endothelial monolayer. Finally, the microfluidic system is utilized to demonstrate extravasation of MDA-MB-231 cancer cells in the presence of CXCL12 chemokine gradients. Consistent with the hypothesis of organ-specific extravasation, control experiments are presented to substantiate the observation that the MDA-MB-231 cell migration is attributed to chemotaxis rather than a random process.