Mao Sifeng, Zhang Qiang, Li Haifang, Zhang Wanling, Huang Qiushi, Khan Mashooq, Lin Jin-Ming
Department of Chemistry , Beijing Key Laboratory of Microanalytical Methods and Instrumentation , MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Tsinghua University , Beijing 100084 , China . Email:
Chem Sci. 2018 Aug 13;9(39):7694-7699. doi: 10.1039/c8sc03027h. eCollection 2018 Oct 21.
Circulating Tumor Cell (CTC) adhesion is essential in understanding the mechanism of metastasis. Although conventional methods for measuring adhesion strength have performed well on cell populations, a deeper insight into cell behavior demands new approaches for realizing non-destructive, high-resolution, analysis of single cell adhesion. Here, we present a microfluidic method for adhesion strength analysis of single CTCs on a base layer of endothelial cells (ECs) to clarify cell-to-cell adhesion at single cell resolution. A confined flow in open space formed by a microfluidic device supplied a trypsin zone for the analysis of single cell adhesion. Tumor cell lines were used to model CTCs. This method was proved successful for extracting different types of CTCs from an endothelial cell layer to measure their adhesion strength by the time required for detachment. Moreover, we successfully uncovered the drug influence on the adhesion strength of single CTCs on ECs, which is promising in drug screening for tumor therapy. The current work reports a general strategy for cell-to-cell adhesion analysis for single cells.
循环肿瘤细胞(CTC)的黏附对于理解转移机制至关重要。尽管传统的测量黏附强度的方法在细胞群体上表现良好,但要更深入地了解细胞行为,就需要新的方法来实现对单细胞黏附的无损、高分辨率分析。在此,我们提出一种微流控方法,用于分析单个CTC在内皮细胞(EC)基层上的黏附强度,以在单细胞分辨率下阐明细胞间黏附。微流控装置在开放空间中形成的受限流提供了一个用于分析单细胞黏附的胰蛋白酶区域。使用肿瘤细胞系来模拟CTC。该方法被证明成功地从内皮细胞层中提取出不同类型的CTC,并通过脱离所需时间来测量它们的黏附强度。此外,我们成功揭示了药物对单个CTC与EC黏附强度的影响,这在肿瘤治疗药物筛选方面具有前景。当前的工作报道了一种用于单细胞间黏附分析的通用策略。