Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Lab Chip. 2018 Jul 10;18(14):2055-2064. doi: 10.1039/c8lc00310f.
Tumors can shed thousands of cells into the circulation daily. These circulating tumor cells (CTCs) are heterogeneous, and their phenotypes change dynamically. Real-time monitoring of CTC phenotypes is crucial to elucidate the role of CTCs in the metastatic cascade. Here, we monitor phenotypic changes in CTCs in mice xenografted with tumors with varying aggressiveness during cancer progression and a course of chemotherapy to study the metastatic potential of CTCs and changes in the properties of these cells in response to treatment. A new device that enables magnetic ranking cytometry (MagRC) is employed to profile the phenotypic properties of CTCs. Overall, CTCs from metastatic xenografts in mice display dynamic and heterogeneous profiles while non-metastatic models had static profiles. Decreased heterogeneity followed by a reduction in metastasis incidence was observed after a course of chemotherapy administered to highly metastatic xenografts. Phenotypic profiling of CTCs could be employed to monitor disease progression and predict therapeutic responses.
肿瘤每天可向循环系统中释放数千个细胞。这些循环肿瘤细胞(CTC)具有异质性,其表型动态变化。实时监测 CTC 表型对于阐明 CTC 在转移级联反应中的作用至关重要。在这里,我们在肿瘤异种移植小鼠中监测了在癌症进展过程中和化疗过程中具有不同侵袭性的肿瘤中 CTC 表型的变化,以研究 CTC 的转移潜力以及这些细胞对治疗的反应特性的变化。一种新的装置可实现磁性排序细胞术(MagRC),用于分析 CTC 的表型特性。总体而言,来自具有转移性异种移植小鼠的 CTC 显示出动态和异质性的特征,而非转移性模型具有静态特征。在对高转移性异种移植小鼠进行化疗后,观察到异质性降低,随后转移发生率降低。CTC 的表型分析可用于监测疾病进展并预测治疗反应。