Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry
Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry
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DOI：
10.1016/j.aca.2019.12.033
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发表时间：
2020-03-08
影响因子：
6.2
通讯作者：
Swami, N. S.
中科院分区：
文献类型：
--
作者：
McGrath, J. S.;Honrado, C.;Swami, N. S.
胰腺导管腺癌（PDAC）是一种侵袭性癌症，缺乏与疾病发作、促进和进展相关的特异性生物标志物。为了评估肿瘤细胞电生理学是否可以作为PDAC致瘤性的标志物，我们使用高通量（类似于350个细胞/s）的多频阻抗细胞术来测量来自异种移植物的单个PDAC肿瘤细胞的电表型，这些肿瘤细胞来自不同患者的原发性胰腺肿瘤与肝转移瘤。一种新的相位对比度度量的基础上的变化，在高，低频率的阻抗相位响应，这是相关的细胞内部的电生理学被发现系统地改变作为致瘤性的函数。较高致瘤性的PDAC细胞表现出较低的内部电导率和增强的介电常数，这是通过对相应的细胞类型的介电电泳验证。使用遗传分析，我们建议的作用，失调的Na+运输和Ca 2+离子从细胞质中去除的关键致癌KRAS驱动的过程，可能是负责降低内部细胞电导率。我们设想，阻抗细胞术可以作为一种工具，以量化表型异质性快速分层致瘤性。它还可以帮助介电泳分离具有特定表型的细胞的方案，用于患者生存的预后研究，并为特定患者定制治疗选择。(C)2019爱思唯尔B. V.保留所有权利。
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer lacking specific biomarkers that can be correlated to disease onset, promotion and progression. To assess whether tumor cell electrophysiology may serve as a marker for PDAC tumorigenicity, we use multi-frequency impedance cytometry at high throughput (similar to 350 cells/s) to measure the electrical phenotype of single PDAC tumor cells from xenografts, which are derived from primary pancreatic tumors versus those from liver metastases of different patients. A novel phase contrast metric based on variations in the high and low frequency impedance phase responses that is related to electrophysiology of the cell interior is found to be systematically altered as a function of tumorigenicity. PDAC cells of higher tumorigenicity exhibited lowered interior conductivity and enhanced permittivity, which is validated by the dielectrophoresis on the respective cell types. Using genetic analysis, we suggest the role of dysregulated Na+ transport and removal of Ca2+ ions from the cytoplasm on key oncogenic KRAS-driven processes that may be responsible for lowering of the interior cell conductivity. We envision that impedance cytometry can serve as a tool to quantify phenotypic heterogeneity for rapidly stratifying tumorigenicity. It can also aid in protocols for dielectrophoretic isolation of cells with a particular phenotype for prognostic studies on patient survival and to tailor therapy selection to specific patients. (C) 2019 Elsevier B.V. All rights reserved.