Ural Evran E, Toomajian Victoria, Hoque Apu Ehsanul, Veletic Mladen, Balasingham Ilangko, Ashammakhi Nureddin, Kanada Masamitsu, Contag Christopher H
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48823, USA.
Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48823, USA.
Int J Mol Sci. 2021 Apr 30;22(9):4784. doi: 10.3390/ijms22094784.
Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.
细胞外囊泡（EVs）是源自细胞的纳米结构，在正常组织和癌症中通过传递复杂信号介导细胞间通讯。肿瘤发生和维持所需的细胞协调部分是通过将分子货物通过细胞外囊泡运输到驻留细胞和远处细胞来介导的。大多数关于细胞外囊泡介导信号传导的研究都是在二维（2D）单层细胞培养中进行的，这主要是因为其简单性和高通量筛选能力。三维（3D）细胞培养可用于研究细胞间和细胞与基质间的相互作用，从而能够研究细胞外囊泡介导的细胞通讯。3D培养可能最适合模拟细胞外囊泡在肿瘤微环境（TME）形成以及维持肿瘤生长的癌细胞与基质相互作用中的作用。在这篇综述中，我们讨论了3D培养中与TME相关的细胞外囊泡生物学。这包括TME中细胞类型之间的细胞外囊泡通讯、与不同支架选择以及无支架3D培养和转移前生态位培养相关的细胞外囊泡生物发生和信号传导差异。对3D TME内细胞外囊泡生物发生和信号传导的理解将改善肿瘤发生的培养相关性，实现对TME的分子控制，并有助于开发基于细胞外囊泡介导信号传导的药物递送工具。
