Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
Angew Chem Int Ed Engl. 2017 Jan 2;56(1):163-168. doi: 10.1002/anie.201608983. Epub 2016 Nov 29.
During cancer progression, tumors shed circulating tumor cells (CTCs) into the bloodstream. CTCs that originate from the same primary tumor can have heterogeneous phenotypes and, while some CTCs possess benign properties, others have high metastatic potential. Deconstructing the heterogeneity of CTCs is challenging and new methods are needed that can sort small numbers of cancer cells according to their phenotypic properties. Here we describe a new microfluidic approach that profiles, along two independent phenotypic axes, the behavior of heterogeneous cell subpopulations. Cancer cells are first profiled according to expression of a surface marker using a nanoparticle-enabled approach. Along the second dimension, these subsets are further separated into subpopulations corresponding to migration profiles generated in response to a chemotactic agent. We deploy this new technique and find a strong correlation between the surface expression and migration potential of CTCs present in blood from mice with xenografted tumors. This system provides an important new means to characterize functional diversity in circulating tumor cells.
在癌症进展过程中，肿瘤会将循环肿瘤细胞（CTC）释放到血液中。源自同一原发性肿瘤的 CTC 可能具有异质性表型，虽然一些 CTC 具有良性特性，但其他 CTC 具有高转移潜能。解析 CTC 的异质性具有挑战性，需要新的方法，根据其表型特性对少量癌细胞进行分类。在这里，我们描述了一种新的微流控方法，可以沿着两个独立的表型轴对异质细胞亚群的行为进行分析。首先，使用纳米颗粒增强的方法根据表面标志物的表达对癌细胞进行分析。沿着第二个维度，这些亚群进一步分为与响应趋化剂产生的迁移谱相对应的亚群。我们采用这种新技术，发现了在异种移植肿瘤小鼠血液中存在的 CTC 的表面表达和迁移潜力之间的强相关性。该系统为表征循环肿瘤细胞中的功能多样性提供了一种重要的新手段。
