Dynamic physical properties of dissociated tumor cells revealed by dielectrophoretic field-flow fractionation.
Dynamic physical properties of dissociated tumor cells revealed by dielectrophoretic field-flow fractionation.
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DOI：
10.1039/c1ib00032b
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Hale KS
中科院分区：
文献类型：
--
作者：
Shim S;Gascoyne P;Noshari J;Hale KS
转移性疾病由癌细胞从实体原发性肿瘤脱落、它们作为循环肿瘤细胞（CTC）通过心血管系统的运输以及它们在远端部位的植入和生长引起。当肿瘤细胞离开其生长部位并作为单细胞移动时，对肿瘤细胞的性质和命运知之甚少。应用分析型介电泳场流分离技术（dFFF）研究了肿瘤细胞的膜电容、密度、流体力学性质以及肿瘤细胞的大小和形态。脱离后，肿瘤细胞表现出生物物理特性，随着时间的推移，通过细胞质脱落的过程，从而失去膜和细胞质。该过程似乎与细胞凋亡、失巢凋亡和坏死的细胞死亡机制不同，并且其可以解释为什么在从患者分离的CTC中以及在从患者的腹水获得的肿瘤细胞中观察到多种表型。动态生物物理特性和细胞质损失CTC迁移到小血管中的循环系统，生存和基因表达的影响进行了讨论。由于肿瘤细胞的总电容即使在它们已经脱落细胞质之后仍然高于血细胞，因此dFFF提供了一种引人注目的、抗体非依赖性的技术，用于从血液中分离活的CTC，即使它们不大于外周血单核细胞。
Metastatic disease results from the shedding of cancer cells from a solid primary tumor, their transport through the cardiovascular system as circulating tumor cells (CTCs) and their engraftment and growth at distant sites. Little is known about the properties and fate of tumor cells as they leave their growth site and travel as single cells. We applied analytical dielectrophoretic field-flow fractionation (dFFF) to study the membrane capacitance, density and hydrodynamic properties together with the size and morphology of cultured tumor cells after they were harvested and placed into single cell suspensions. After detachment, the tumor cells exhibited biophysical properties that changed with time through a process of cytoplasmic shedding whereby membrane and cytoplasm were lost. This process appeared to be distinct from the cell death mechanisms of apoptosis, anoikis and necrosis and it may explain why multiple phenotypes are seen among CTCs isolated from patients and among the tumor cells obtained from ascitic fluid of patients. The implications of dynamic biophysical properties and cytoplasmic loss for CTC migration into small blood vessels in the circulatory system, survival and gene expression are discussed. Because the total capacitance of tumor cells remained higher than blood cells even after they had shed cytoplasm, dFFF offers a compelling, antibody-independent technology for isolating viable CTCs from blood even when they are no larger than peripheral blood mononuclear cells.
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