Fluorometric Quantification of Single-Cell Velocities to Investigate Cancer Metastasis
Fluorometric Quantification of Single-Cell Velocities to Investigate Cancer Metastasis
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DOI：
10.1016/j.cels.2018.10.005
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发表时间：
2018-11-28
期刊：
影响因子：
9.3
通讯作者：
Thomas, Susan Napier
中科院分区：
文献类型：
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作者：
Edwards, Erin Elizabeth;Birmingham, Katherine Gayle;Thomas, Susan Napier
血行转移是一个多步骤的、选择素调控的过程，其机制尚不清楚。为了研究这种癌症扩散的生物学途径，并更好地了解循环癌细胞，我们开发了一种高通量方法，将类似于芯片器官的微流控和光可转化蛋白质技术结合在一起。我们的方法可以归因于单细胞速度作为可追踪的细胞属性，用于在生理相关的流体流动的背景下分析细胞分子轮廓和粘附性表型之间的直接关系。我们询问了自然表达的选择素配体与结肠癌细胞滚动频率和速度的关系，并为先前报道的选择素介导的黏附和转移的体外和体内模型中的差异提供了背景。这一综合方法学代表了一种开发抗转移疗法的通用方法，以及生成和测试关于发生在几秒钟到几小时的时间尺度上的单细胞分辨率的时空过程的机械性假说。
Hematogenous metastasis is a multistep, selectin-regulated process whose mechanisms remain poorly understood. To investigate this biological pathway of cancer dissemination and better understand circulating cancer cells, we developed a high-throughput methodology that integrates organ-on-chip-like microfluidic and photoconvertible protein technologies. Our approach can ascribe single-cell velocity as a traceable cell property for off-chip analysis of the direct relationships between cell molecular profiles and adhesive phenotypes in the context of physiologically relevant fluid flow. We interrogate how natively expressed selectin ligands relate to colon cancer cell rolling frequencies and velocities and provide context for previously reported disparities in in vitro and in vivo models of selectin-mediated adhesion and metastasis. This integrated methodology represents a versatile approach for the development of anti-metastatic therapeutics as well as to generate and test mechanistic hypotheses regarding spatiotemporal processes that occur over timescales of seconds to hours with single-cell resolution.