Department of Imaging Physics Unit 951, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Integr Biol (Camb). 2011 Aug;3(8):850-62. doi: 10.1039/c1ib00032b. Epub 2011 Jun 21.
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.
转移性疾病源于实体原发性肿瘤中癌细胞的脱落，它们作为循环肿瘤细胞（CTCs）通过心血管系统运输，并在远处部位定植和生长。关于离开生长部位并作为单细胞迁移的肿瘤细胞的特性和命运，人们知之甚少。我们应用分析性介电泳场流分离（dFFF）技术来研究培养的肿瘤细胞在收获并置于单细胞悬浮液中后的膜电容、密度和流体动力学特性，以及大小和形态。分离后，肿瘤细胞表现出随时间变化的生物物理特性，这是一个通过细胞质脱落的过程，在此过程中，细胞膜和细胞质丢失。这个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，它可能解释了为什么从患者中分离出的 CTC 以及从患者腹水获得的肿瘤细胞中会出现多种表型。还讨论了动态生物物理特性和细胞质损失对 CTC 迁移到循环系统中小血管、存活和基因表达的影响。因为即使肿瘤细胞已经失去了细胞质，其总电容仍然高于血细胞，所以即使 CTC 与外周血单核细胞一样小，dFFF 也提供了一种令人信服的、不依赖抗体的技术来从血液中分离出有活力的 CTC。
