P D Patel Institute of Applied Sciences, Charotar University of Science and Technology (CHARUSAT), Changa 388 421, India.
Dr. K C Patel Research and Development Centre, University Research Centre(s), Charotar University of Science and Technology (CHARUSAT), Changa 388 421, India.
Life Sci. 2024 Dec 1;358:123184. doi: 10.1016/j.lfs.2024.123184. Epub 2024 Oct 28.
In the attempts to mitigate uncertainties in the results of monolayer culture for the identification of cancer therapeutic targets and compounds, there has been a growing interest in using 3D cancer spheroid models, which include tumorospheres (TSs), tissue-derived tumor spheres (TDTSs), organotypic multicellular tumor spheroids (OMSs), and multicellular tumor spheroids (MCTSs). The MCTSs, either Mono-MCTSs or Hetero-MCTSs, with or without scaffold, in particular, offer numerous advantages over other spheroid models, including easy cultivation, high reproducibility, accessibility, high throughput, controllable size, well-rounded shape, simplicity of genetic manipulation, economical and availability of various biological methods for their development. In this review, we have attempted to discuss the role of MCTSs concerning various aspects of translational cancer research, such as drug response and penetration, cell-cell interaction, and invasion and metastasis. However, the Mono-MCTSs, either scaffold-free or scaffold-based, may not adequately represent the cellular heterogeneity and complexity of clinical tumors, limiting their utility in translational cancer research. Conversely, Hetero-MCTS models, both scaffold-free and scaffold-based, show better suitability due to the presence of a similar in vivo type tumor microenvironment. Nonetheless, scaffold-based Hetero-MCTS models show batch variability and challenges in performing quantitative assays due to difficulties extracting spheroids and cells from scaffolds. Further, incorporating stromal cells with cancer cells in a more precise ratio to develop Hetero-MCTSs can enhance the model's relevance, yielding more clinically reliable outcomes for drug candidates and improving insights into tumor biology.
为了减少单层培养在鉴定癌症治疗靶点和化合物方面结果的不确定性，人们越来越感兴趣地使用 3D 癌症球体模型，包括肿瘤球体（TSs）、组织来源的肿瘤球体（TDTSs）、器官型多细胞肿瘤球体（OMSs）和多细胞肿瘤球体（MCTSs）。MCTSs，无论是单 MCTSs 还是异质 MCTSs，有或没有支架，特别是提供了许多优于其他球体模型的优势，包括易于培养、高重现性、可及性、高通量、可控大小、圆润形状、遗传操作的简单性、经济性和可用于其开发的各种生物学方法。在这篇综述中，我们试图讨论 MCTSs 在癌症转化研究的各个方面的作用，如药物反应和渗透、细胞-细胞相互作用以及侵袭和转移。然而，单 MCTSs，无论是无支架还是有支架，可能不能充分代表临床肿瘤的细胞异质性和复杂性，限制了它们在癌症转化研究中的应用。相反，异质 MCTS 模型，无论是无支架还是有支架，由于存在类似于体内类型的肿瘤微环境，显示出更好的适用性。尽管如此，由于从支架中提取球体和细胞存在困难，基于支架的异质 MCTS 模型显示出批次可变性和定量测定的挑战。此外，将基质细胞与癌细胞以更精确的比例合并到异质 MCTS 中可以增强模型的相关性，为候选药物提供更具临床可靠性的结果，并深入了解肿瘤生物学。
