Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA; Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, 14853, USA.
Curr Opin Cell Biol. 2021 Oct;72:1-9. doi: 10.1016/j.ceb.2021.04.001. Epub 2021 May 12.
Intratumoral heterogeneity is a negative prognostic factor for cancer and commonly attributed to microenvironment-driven genetic mutations and/or the emergence of cancer stem-like cells. How aberrant extracellular matrix (ECM) remodeling regulates the phenotypic diversity of tumor cells, however, remains poorly understood due in part to a lack of model systems that allow isolating the physicochemical heterogeneity of malignancy-associated ECM for mechanistic studies. Here, we review the compositional, microarchitectural, and mechanical hallmarks of cancer-associated ECM and highlight biomaterials and engineering approaches to recapitulate these properties for in vitro and in vivo studies. Subsequently, we describe how such engineered platforms may be explored to define the spatiotemporal dynamics through which cancer-associated ECM remodeling regulates intratumoral heterogeneity and the cancer stem-like cell phenotype. Finally, we highlight future opportunities and technological advances to further elucidate the relationship between tumor-associated ECM dynamics and intratumoral heterogeneity.
肿瘤内异质性是癌症的一个负面预后因素，通常归因于微环境驱动的基因突变和/或癌症干细胞样细胞的出现。然而，由于缺乏允许分离与恶性相关的细胞外基质的物理化学异质性以进行机制研究的模型系统，因此对于异常细胞外基质（ECM）重塑如何调节肿瘤细胞表型多样性仍知之甚少。在这里，我们回顾了与癌症相关的 ECM 的组成、微观结构和力学特征，并强调了生物材料和工程方法，以重现这些特性，用于体外和体内研究。随后，我们描述了如何探索这些工程平台，以定义通过肿瘤相关 ECM 重塑调节肿瘤内异质性和癌症干细胞样细胞表型的时空动力学。最后，我们强调了未来的机会和技术进步，以进一步阐明肿瘤相关 ECM 动力学与肿瘤内异质性之间的关系。
