Mohammadalipour A, Burdick M M, Tees D F J
1Department of Physics and Astronomy, Ohio University, Athens, OH 45701 USA.
2Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH 45701 USA.
Cell Mol Bioeng. 2017 Apr 3;10(3):235-248. doi: 10.1007/s12195-017-0485-8. eCollection 2017 Jun.
Defining the characteristics of cancer stem cells (CSC) has become an important subject in cancer research during the past decade. Although molecular surface expression levels have been used for CSC recognition, the clinical and prognostic impacts of these markers have remained a controversial issue. The finding that cancerous cells are considerably more deformable than normal ones provides the motivation for the hypothesis that the mechanical properties can be used as biomarkers to distinguish between stem-like and non-stem-like cancer cells. In this study, using micropipette aspiration (MA) and intracellular particle tracking (IPT) microrheology, measurements of the whole-cell and local viscoelasticity were made on four breast cancer cell lines with different CSC phenotypes based on their surface markers. Stem-like Hs578T and MDA-MB-231 cell lines were found to be the most deformable, while the non-stem-like MDA-MB-468 line was the least deformable. The non-stem-like BT-20 cell line showed an intermediate deformability. The enhanced deformability for stem-like cells was consistent with the observed lower and more dispersed F-actin content for the stem-like cells. Therefore, the cytoskeleton-related differences in the rheological properties of cancer cells can be a potential biomarker for CSC and eventually lead to novel cancer diagnostic and therapeutic methods.
在过去十年中,定义癌症干细胞(CSC)的特征已成为癌症研究中的一个重要课题。尽管分子表面表达水平已被用于识别CSC,但这些标志物的临床和预后影响仍然是一个有争议的问题。癌细胞比正常细胞更具可变形性这一发现,为机械性能可作为区分干细胞样和非干细胞样癌细胞的生物标志物这一假设提供了动力。在本研究中,使用微量吸管抽吸(MA)和细胞内颗粒追踪(IPT)微流变学,对基于表面标志物具有不同CSC表型的四种乳腺癌细胞系进行了全细胞和局部粘弹性测量。发现干细胞样的Hs578T和MDA-MB-231细胞系最具可变形性,而非干细胞样的MDA-MB-468细胞系可变形性最小。非干细胞样的BT-20细胞系表现出中等的可变形性。干细胞样细胞增强的可变形性与观察到的干细胞样细胞中较低且更分散的F-肌动蛋白含量一致。因此,癌细胞流变特性中与细胞骨架相关的差异可能是CSC的潜在生物标志物,并最终导致新的癌症诊断和治疗方法。