Cui Xin, Guo Weijin, Sun Yubing, Sun Baoce, Hu Shuhuan, Sun Dong, Lam Raymond H W
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong.
Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01002, USA.
Biomicrofluidics. 2017 Jan 13;11(1):014105. doi: 10.1063/1.4974012. eCollection 2017 Jan.
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.
癌细胞的跨内皮迁移是包括乳腺癌在内的癌症发展过程中的一个关键阶段,因为迁移的细胞通常被认为具有高度转移性。然而,对于许多现有平台而言,要实现完全覆盖的内皮细胞层并确保提取的癌细胞具有跨内皮迁移能力以进行高特异性分析,仍然具有挑战性。在此,我们报告了一种微流控装置,该装置在嵌入式内皮细胞层下方包含多个独立的细胞收集微腔,从而可以仅从内皮细胞层完全覆盖的微腔中选择性收集跨内皮迁移的细胞。在这项工作中,我们首先优化了用于形成内皮细胞层的微制造支撑膜的孔径。我们量化了恶性人乳腺癌细胞系(MDA-MB-231)在不同剪切应力水平下的跨内皮迁移率。我们研究了迁移细胞的特征,包括形态、细胞骨架结构以及迁移情况(速度和持续性)。这种嵌入式内皮微流控装置的进一步应用可以为与癌症转移相关的迁移和细胞内特征以及有效的癌症治疗策略提供重要见解。