Department of Biomedical Engineering, Cornell University, Ithaca, New York.
Am J Physiol Cell Physiol. 2014 Jan 15;306(2):C110-20. doi: 10.1152/ajpcell.00283.2013. Epub 2013 Nov 6.
The tumor microenvironment is a milieu of heterogeneous architectural features that affect tumor growth and metastatic invasion. Pore size, density, stiffness, and fiber architecture change dramatically from location to location throughout the tumor matrix. While many studies have addressed the effects of two-dimensional extracellular matrix structure and composition on cell migration, less is known about how cancer cells navigate complex, heterogeneous three-dimensional (3D) microenvironments. Mechanical structures such as actin and keratin, part of the cytoskeletal framework, and lamins, part of the nucleoskeletal framework, play a key role in migration and are altered during cancer progression. Recent evidence suggests that these changes in cytoskeletal and nucleoskeletal structures may enable cancer cells to efficiently respond to features such as pore size and stiffness to invade and migrate. Here we discuss the role of cell mechanics and the cytoskeleton in the ability of cells to navigate and respond to 3D matrix features and heterogeneities.
肿瘤微环境是一个异质结构的环境，会影响肿瘤的生长和转移侵袭。肿瘤基质中，孔的大小、密度、硬度和纤维结构从一个位置到另一个位置都发生了显著的变化。虽然许多研究已经研究了二维细胞外基质结构和组成对细胞迁移的影响，但对于癌细胞如何在复杂的、异质的三维（3D）微环境中导航的了解较少。细胞骨架中的肌动蛋白和角蛋白等机械结构以及核骨架中的层粘连蛋白等结构在迁移中起着关键作用，并且在癌症进展过程中会发生改变。最近的证据表明，细胞骨架和核骨架结构的这些变化可能使癌细胞能够有效地响应孔径和硬度等特征，从而进行侵袭和迁移。在这里，我们讨论了细胞力学和细胞骨架在细胞导航和响应 3D 基质特征和异质性方面的作用。
