Institute of Biophysics, Department of Bionanosciences, University of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria.
Cancer Heterogeneity Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain.
Int J Mol Sci. 2023 Jul 30;24(15):12208. doi: 10.3390/ijms241512208.
In healthy tissues, cells are in mechanical homeostasis. During cancer progression, this equilibrium is disrupted. Cancer cells alter their mechanical phenotype to a softer and more fluid-like one than that of healthy cells. This is connected to cytoskeletal remodeling, changed adhesion properties, faster cell proliferation and increased cell motility. In this work, we investigated the mechanical properties of breast cancer cells representative of different breast cancer subtypes, using MCF-7, tamoxifen-resistant MCF-7, MCF10A and MDA-MB-231 cells. We derived viscoelastic properties from atomic force microscopy force spectroscopy measurements and showed that the mechanical properties of the cells are associated with cancer cell malignancy. MCF10A are the stiffest and least fluid-like cells, while tamoxifen-resistant MCF-7 cells are the softest ones. MCF-7 and MDA-MB-231 show an intermediate mechanical phenotype. Confocal fluorescence microscopy on cytoskeletal elements shows differences in actin network organization, as well as changes in focal adhesion localization. These findings provide further evidence of distinct changes in the mechanical properties of cancer cells compared to healthy cells and add to the present understanding of the complex alterations involved in tumorigenesis.
在健康的组织中，细胞处于力学平衡状态。在癌症进展过程中，这种平衡被打破。癌细胞改变了它们的力学表型，变得比健康细胞更柔软、更具流动性。这与细胞骨架重塑、改变的粘附特性、更快的细胞增殖和增加的细胞迁移性有关。在这项工作中，我们使用 MCF-7、他莫昔芬耐药 MCF-7、MCF10A 和 MDA-MB-231 细胞，研究了不同乳腺癌亚型代表的乳腺癌细胞的力学特性。我们从原子力显微镜力谱测量中得出粘弹性特性，并表明细胞的力学特性与癌细胞的恶性程度有关。MCF10A 是最硬、最不易流动的细胞，而他莫昔芬耐药 MCF-7 细胞则是最柔软的细胞。MCF-7 和 MDA-MB-231 表现出中间力学表型。细胞骨架元素的共聚焦荧光显微镜显示出肌动蛋白网络组织的差异，以及焦点粘连定位的变化。这些发现进一步证明了与健康细胞相比，癌细胞的力学特性发生了明显的变化，并增加了对肿瘤发生过程中涉及的复杂变化的现有理解。
