Depterment of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129 Milano, Italy.
Int J Mol Sci. 2021 Feb 5;22(4):1633. doi: 10.3390/ijms22041633.
Two-dimensional (2D) cell cultures have been the standard for many different applications, ranging from basic research to stem cell and cancer research to regenerative medicine, for most of the past century. Hence, almost all of our knowledge about fundamental biological processes has been provided by primary and established cell lines cultured in 2D monolayer. However, cells in tissues and organs do not exist as single entities, and life in multicellular organisms relies on the coordination of several cellular activities, which depend on cell-cell communication across different cell types and tissues. In addition, cells are embedded within a complex non-cellular structure known as the extracellular matrix (ECM), which anchors them in a three-dimensional (3D) formation. Likewise, tumour cells interact with their surrounding matrix and tissue, and the physical and biochemical properties of this microenvironment regulate cancer differentiation, proliferation, invasion, and metastasis. 2D models are unable to mimic the complex and dynamic interactions of the tumour microenvironment (TME) and ignore spatial cell-ECM and cell-cell interactions. Thus, multicellular 3D models are excellent tools to recapitulate in vitro the spatial dimension, cellular heterogeneity, and molecular networks of the TME. This review summarizes the biological significance of the cell-ECM and cell-cell interactions in the onset and progression of tumours and focuses on the requirement for these interactions to build up representative in vitro models for the study of the pathophysiology of cancer and for the design of more clinically relevant treatments.
二维（2D）细胞培养在过去的一个世纪中一直是许多不同应用的标准，从基础研究到干细胞和癌症研究到再生医学。因此，我们对基本生物学过程的几乎所有了解都是通过在 2D 单层中培养的原代和已建立的细胞系提供的。然而，组织和器官中的细胞并不是单独存在的，多细胞生物的生命依赖于几种细胞活动的协调，这取决于不同细胞类型和组织之间的细胞间通讯。此外，细胞嵌入在称为细胞外基质（ECM）的复杂非细胞结构中，该结构将它们锚定在三维（3D）结构中。同样，肿瘤细胞与其周围基质和组织相互作用，并且微环境的物理和生化特性调节着癌症的分化、增殖、侵袭和转移。2D 模型无法模拟肿瘤微环境（TME）的复杂和动态相互作用，并且忽略了空间细胞-ECM 和细胞-细胞相互作用。因此，多细胞 3D 模型是体外重现 TME 的空间维度、细胞异质性和分子网络的出色工具。这篇综述总结了细胞-ECM 和细胞-细胞相互作用在肿瘤发生和进展中的生物学意义，并重点介绍了这些相互作用对于建立用于研究癌症病理生理学和设计更具临床相关性的治疗方法的代表性体外模型的必要性。
