Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
Adv Drug Deliv Rev. 2014 Apr;69-70:29-41. doi: 10.1016/j.addr.2014.03.001. Epub 2014 Mar 15.
Phenotypic heterogeneity of cancer cells, cell biological context, heterotypic crosstalk and the microenvironment are key determinants of the multistep process of tumor development. They sign responsible, to a significant extent, for the limited response and resistance of cancer cells to molecular-targeted therapies. Better functional knowledge of the complex intra- and intercellular signaling circuits underlying communication between the different cell types populating a tumor tissue and of the systemic and local factors that shape the tumor microenvironment is therefore imperative. Sophisticated 3D multicellular tumor spheroid (MCTS) systems provide an emerging tool to model the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth. In this review we discuss the cellular, chemical and physical factors contributing to zonation and cellular crosstalk within tumor masses. On this basis, we further describe 3D cell culture technologies for growth of MCTS as advanced tools for exploring molecular tumor growth determinants and facilitating drug discovery efforts. We conclude with a synopsis on technological aspects for on-line analysis and post-processing of 3D MCTS models.
肿瘤细胞的表型异质性、细胞生物学背景、异质性串扰和微环境是肿瘤发展多步骤过程的关键决定因素。它们在很大程度上负责解释癌细胞对分子靶向治疗的反应有限和耐药性。因此，深入了解构成肿瘤组织中不同细胞类型之间通讯的复杂细胞内和细胞间信号转导回路以及塑造肿瘤微环境的系统和局部因素至关重要。复杂的三维多细胞肿瘤球体（MCTS）系统提供了一种新兴的工具，可用于模拟体内肿瘤生长的表型和细胞异质性以及微环境方面。在本文中，我们讨论了导致肿瘤内分区和细胞串扰的细胞、化学和物理因素。在此基础上，我们进一步描述了用于 MCTS 生长的 3D 细胞培养技术，作为探索分子肿瘤生长决定因素和促进药物发现工作的先进工具。最后，我们概述了 3D MCTS 模型的在线分析和后处理的技术方面。
