Jiang Kuan, Liang Lanfeng, Lim Chwee Teck
Mechanobiology Institute, National University of Singapore, Singapore.
Department of Biomedical Engineering, National University of Singapore, Singapore.
iScience. 2021 Jan 27;24(2):102098. doi: 10.1016/j.isci.2021.102098. eCollection 2021 Feb 19.
The physical microenvironment of cells plays a fundamental role in regulating cellular behavior and cell fate, especially in the context of cancer metastasis. For example, capillary deformation can destroy arrested circulating tumor cells while the dense extracellular matrix can form a physical barrier for invading cancer cells. Understanding how metastatic cancer cells overcome the challenges brought forth by physical confinement can help in developing better therapeutics that can put a stop to this migratory stage of the metastatic cascade. Numerous and assays have been developed to recapitulate the metastatic processes and study cancer cell migration in a confining microenvironment. In this review, we summarize some of the representative techniques and the exciting new findings. We critically review the advantages, as well as challenges associated with these tools and methodologies, and provide a guide on the applications that they are most suited for. We hope future efforts that push forward our current understanding on metastasis under confinement can lead to novel and more effective diagnostic and therapeutic strategies against this dreaded disease.
细胞的物理微环境在调节细胞行为和细胞命运方面起着基础性作用，尤其是在癌症转移的背景下。例如，毛细血管变形可破坏停滞的循环肿瘤细胞，而致密的细胞外基质可为侵袭性癌细胞形成物理屏障。了解转移性癌细胞如何克服物理限制带来的挑战，有助于开发更好的疗法，从而阻止转移级联反应的这一迁移阶段。已经开发了许多实验和分析方法来重现转移过程，并研究癌细胞在受限微环境中的迁移。在本综述中，我们总结了一些代表性技术和令人兴奋的新发现。我们批判性地审视了这些工具和方法的优点以及相关挑战，并提供了它们最适合应用的指南。我们希望未来推动我们目前对受限条件下转移理解的努力能够带来针对这种可怕疾病的新颖且更有效的诊断和治疗策略。
