Fox Chase Cancer Center, Cancer Biology, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
Semin Cancer Biol. 2010 Jun;20(3):139-45. doi: 10.1016/j.semcancer.2010.04.004. Epub 2010 May 7.
Tumor progression in vitro has traditionally been studied in the context of two-dimensional (2D) environments. However, it is now well accepted that 2D substrates are unnaturally rigid compared to the physiological substrate known as extracellular matrix (ECM) that is in direct contact with both normal and tumorigenic cells in vivo. Hence, the patterns of interactions, as well as the strategies used by cells in order to penetrate the ECM, and migrate through a three-dimensional (3D) environment are notoriously different than those observed in 2D. Several substrates, such as collagen I, laminin, or complex mixtures of ECM components have been used as surrogates of native 3D ECM to more accurately study cancer cell behaviors. In addition, 3D matrices developed from normal or tumor-associated fibroblasts have been produced to recapitulate the mesenchymal 3D environment that assorted cells encounter in vivo. Some of these substrates are being used to evaluate physico-mechanical effects on tumor cell behavior. Physiological 3D ECMs exhibit a wide range of rigidities amongst different tissues while the degree of stromal stiffness is known to change during tumorigenesis. In this review we describe some of the physico-mechanical characteristics of tumor-associated ECMs believed to play important roles in regulating epithelial tumorigenic behaviors.
肿瘤在体外的进展传统上是在二维（2D）环境中研究的。然而，现在人们普遍认为，与体内正常和致瘤细胞直接接触的生理基质即细胞外基质（ECM）相比，2D 基质异常坚硬。因此，细胞之间相互作用的模式以及细胞穿透 ECM 并在三维（3D）环境中迁移的策略与在 2D 中观察到的明显不同。已经使用了几种基质，如胶原 I、层粘连蛋白或 ECM 成分的复杂混合物，作为天然 3D ECM 的替代品，以更准确地研究癌细胞行为。此外，已经制备了源自正常或肿瘤相关成纤维细胞的 3D 基质，以重现各种细胞在体内遇到的间质 3D 环境。其中一些基质被用于评估对肿瘤细胞行为的物理力学影响。生理 3D ECM 在不同组织之间表现出广泛的硬度范围，而基质硬度的程度已知在肿瘤发生过程中会发生变化。在这篇综述中，我们描述了一些被认为在调节上皮肿瘤发生行为中起重要作用的肿瘤相关 ECM 的物理力学特性。
