Mierke Claudia Tanja
Faculty of Physics and Earth System Sciences, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, 04103 Leipzig, Germany.
Cells. 2025 Apr 12;14(8):584. doi: 10.3390/cells14080584.
Beyond the genomic and proteomic analysis of bulk and single cancer cells, a new focus of cancer research is emerging that is based on the mechanical analysis of cancer cells. Therefore, several biophysical techniques have been developed and adapted. The characterization of cancer cells, like human cancer cell lines, started with their mechanical characterization at mostly a single timepoint. A universal hypothesis has been proposed that cancer cells need to be softer to migrate and invade tissues and subsequently metastasize in targeted organs. Thus, the softness of cancer cells has been suggested to serve as a universal physical marker for the malignancy of cancer types. However, it has turned out that there exists the opposite phenomenon, namely that stiffer cancer cells are more migratory and invasive and therefore lead to more metastases. These contradictory results question the universality of the role of softness of cancer cells in the malignant progression of cancers. Another problem is that the various biophysical techniques used can affect the mechanical properties of cancer cells, making it even more difficult to compare the results of different studies. Apart from the instrumentation, the culture and measurement conditions of the cancer cells can influence the mechanical measurements. The review highlights the main advances of the mechanical characterization of cancer cells, discusses the strength and weaknesses of the approaches, and questions whether the passive mechanical characterization of cancer cells is still state-of-the art. Besides the cell models, conditions and biophysical setups, the role of the microenvironment on the mechanical characteristics of cancer cells is presented and debated. Finally, combinatorial approaches to determine the malignant potential of tumors, such as the involvement of the ECM, the cells in a homogeneous or heterogeneous association, or biological multi-omics analyses, together with the dynamic-mechanical analysis of cancer cells, are highlighted as new frontiers of research.
除了对大量癌细胞和单个癌细胞进行基因组和蛋白质组分析外，基于癌细胞力学分析的癌症研究新焦点正在兴起。因此，已经开发并采用了几种生物物理技术。对癌细胞（如人类癌细胞系）的表征，最初主要是在单个时间点对其进行力学表征。人们提出了一个普遍假设，即癌细胞需要更柔软才能迁移和侵袭组织，随后在靶器官中转移。因此，癌细胞的柔软性被认为是癌症类型恶性程度的通用物理标志物。然而，事实证明存在相反的现象，即更坚硬的癌细胞更具迁移性和侵袭性，因此会导致更多转移。这些相互矛盾的结果质疑了癌细胞柔软性在癌症恶性进展中作用的普遍性。另一个问题是，所使用的各种生物物理技术会影响癌细胞的力学特性，使得不同研究结果的比较更加困难。除了仪器设备外，癌细胞的培养和测量条件也会影响力学测量。本综述强调了癌细胞力学表征的主要进展，讨论了这些方法的优缺点，并质疑癌细胞的被动力学表征是否仍然是当前的前沿技术。除了细胞模型、条件和生物物理设置外，还介绍并讨论了微环境对癌细胞力学特性的作用。最后，确定肿瘤恶性潜能的组合方法，如细胞外基质的参与、同质或异质关联中的细胞，或生物多组学分析，以及癌细胞的动态力学分析，被强调为新的研究前沿。
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