INSERM UMR_S1109, Tumor Biomechanics, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.
Dev Cell. 2021 Jan 25;56(2):164-179. doi: 10.1016/j.devcel.2020.10.011. Epub 2020 Nov 24.
The most dangerous aspect of cancer lies in metastatic progression. Tumor cells will successfully form life-threatening metastases when they undergo sequential steps along a journey from the primary tumor to distant organs. From a biomechanics standpoint, growth, invasion, intravasation, circulation, arrest/adhesion, and extravasation of tumor cells demand particular cell-mechanical properties in order to survive and complete the metastatic cascade. With metastatic cells usually being softer than their non-malignant counterparts, high deformability for both the cell and its nucleus is thought to offer a significant advantage for metastatic potential. However, it is still unclear whether there is a finely tuned but fixed mechanical state that accommodates all mechanical features required for survival throughout the cascade or whether tumor cells need to dynamically refine their properties and intracellular components at each new step encountered. Here, we review the various mechanical requirements successful cancer cells might need to fulfill along their journey and speculate on the possibility that they dynamically adapt their properties accordingly. The mechanical signature of a successful cancer cell might actually be its ability to adapt to the successive microenvironmental constraints along the different steps of the journey.
癌症最危险的方面在于转移进展。当肿瘤细胞沿着从原发性肿瘤到远处器官的连续步骤进行时,它们将成功形成危及生命的转移。从生物力学的角度来看,肿瘤细胞的生长、侵袭、内渗、循环、停滞/黏附以及外渗都需要特定的细胞力学特性,以便存活并完成转移级联反应。由于转移性细胞通常比非恶性细胞柔软,因此人们认为细胞及其核的高变形性为转移潜能提供了显著优势。然而,目前尚不清楚是否存在一种精细调节但固定的机械状态,可以适应整个级联反应中生存所需的所有机械特征,还是肿瘤细胞需要在遇到的每个新步骤中动态地改进其特性和细胞内成分。在这里,我们回顾了成功的癌细胞在其迁移过程中可能需要满足的各种机械要求,并推测它们可能会相应地动态调整其特性。成功的癌细胞的力学特征实际上可能是其适应迁移过程中不同步骤的连续微环境限制的能力。