Biomechanics Laboratory, University Hospital Balgrist, University of Zürich, 8008 Zürich, Switzerland.
Institute for Biomechanics, ETH Zurich, 8008 Zürich, Switzerland.
Mol Biol Cell. 2019 Mar 21;30(7):887-898. doi: 10.1091/mbc.E18-08-0545. Epub 2019 Feb 20.
Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate remains below 30%. In the present work, we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells. With that aim, we used two paired osteosarcoma cell lines, with each one comprising a parental line with low metastatic potential and its experimentally selected, highly metastatic form. Mechanical characterization was performed by means of atomic force microscopy, tensile biaxial deformation, and real-time deformability, and cell traction was measured using two-dimensional and micropost-based traction force microscopy. Our results reveal that the low metastatic osteosarcoma cells display larger spreading sizes and generate higher forces than the experimentally selected, highly malignant variants. In turn, the outcome of cell stiffness measurements strongly depends on the method used and the state of the probed cell, indicating that only a set of phenotyping methods provides the full picture of cell mechanics.
骨肉瘤是最常见的原发性骨肿瘤,其特征是高转移倾向于肺部。虽然早期诊断的治疗结果导致 5 年生存率接近 60%,但诊断时继发病变患者的预后较差,其 5 年生存率仍低于 30%。在本工作中,我们使用了多种分析方法来研究转移潜能增加对骨肉瘤细胞的生物物理特性和力产生的影响。为此,我们使用了两对配对的骨肉瘤细胞系,每一对都包括一个低转移潜能的亲本系及其实验选择的高转移性形式。通过原子力显微镜、拉伸双向变形和实时变形性进行机械特性分析,并使用二维和微柱基牵引力显微镜测量细胞牵引力。我们的结果表明,低转移性骨肉瘤细胞的铺展尺寸较大,产生的力比实验选择的高度恶性变体更大。反过来,细胞刚度测量的结果强烈依赖于所使用的方法和被探测细胞的状态,表明只有一组表型分析方法才能提供细胞力学的全貌。