A microfluidic device for isolation and characterization of transendothelial migrating cancer cells.

A microfluidic device for isolation and characterization of transendothelial migrating cancer cells.
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DOI:
10.1063/1.4974012
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发表时间:
2017-01
期刊:
影响因子:
3.2
通讯作者:
Lam RHW
Lam RHW
中科院分区:
工程技术3区
文献类型:
--
作者:
Cui X;Guo W;Sun Y;Sun B;Hu S;Sun D;Lam RHW

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癌细胞的跨上皮迁移是癌症(包括乳腺癌)的关键阶段,因为通常认为迁移细胞具有高度转移性。然而,对于许多现有的平台来说,实现完全覆盖内皮并确保提取的癌细胞的跨内皮迁移能力以进行高特异性分析仍然具有挑战性。在这里,我们报告了一个微流控装置,包含多个独立的细胞收集微室下的嵌入式内皮,这样的transendothelial-migrated细胞可以选择性地收集从只有微室与内皮层的全覆盖。在这项工作中,我们首先优化的微支撑膜的内皮形成的孔径。我们量化的恶性人类乳腺细胞类型(MDA-MB-231)在不同的剪切应力水平下的跨内皮迁移率。我们研究迁移细胞的特征,包括形态,细胞骨架结构和迁移(速度和持久性)。这种内皮嵌入的微流体装置的进一步实施可以提供与癌症转移相关的迁移和细胞内特征以及有效癌症治疗策略的重要见解。
Transendothelial migration of cancer cells is a critical stage in cancer, including breast cancer, as the migrating cells are generally believed to be highly metastatic. However, it is still challenging for many existing platforms to achieve a fully covering endothelium and to ensure transendothelial migration capability of the extracted cancer cells for analyses with high specificity. Here, we report a microfluidic device containing multiple independent cell collection microchambers underneath an embedded endothelium such that the transendothelial-migrated cells can be selectively collected from only the microchambers with full coverage of an endothelial layer. In this work, we first optimize the pore size of a microfabricated supporting membrane for the endothelium formation. We quantify transendothelial migration rates of a malignant human breast cell type (MDA-MB-231) under different shear stress levels. We investigate characteristics of the migrating cells including morphology, cytoskeletal structures, and migration (speed and persistence). Further implementation of this endothelium-embedded microfluidic device can provide important insights into migration and intracellular characteristics related to cancer metastasis and strategies for effective cancer therapy.
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