Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland.
Tissue Engineering Research Group (TERG), Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Trinity Centre of Bioengineering (TCBE), Trinity College Dublin (TCD), Dublin, Ireland; Dept. of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin (TCD), the University of Dublin, Ireland.
Acta Biomater. 2021 Sep 15;132:360-378. doi: 10.1016/j.actbio.2021.01.023. Epub 2021 Jan 20.
The majority of in vitro studies assessing cancer treatments are performed in two-dimensional (2D) monolayers and are subsequently validated in in vivo animal models. However, 2D models fail to accurately model the tumour microenvironment. Furthermore, animal models are not directly applicable to mimic the human scenario. Three-dimensional (3D) culture models may help to address the discrepancies of 2D and animal models. When cancer cells escape the primary tumour, they can invade at distant organs building secondary tumours, called metastasis. The development of metastasis leads to a dramatic decrease in the life expectancy of patients. Therefore, 3D systems to model the microenvironment of metastasis have also been developed. Several studies have demonstrated changes in cell behaviour and gene expression when cells are cultured in 3D compared to 2D and concluded a better comparability to cells in vivo. Of special importance is the effect seen in response to anti-cancer treatments as models are built primarily to serve as drug-testing platforms. This review highlights these changes between cancer cells grown in 2D and 3D models for some of the most common cancers including lung, breast and prostate tumours. In addition to models aiming to mimic the primary tumour site, the effects of 3D cell culturing in bone metastasis models are also described. STATEMENT OF SIGNIFICANCE: Most in vitro studies in cancer research are performed in 2D and are subsequently validated in in vivo animal models. However, both models possess numerous limitations: 2D models fail to accurately model the tumour microenvironment while animal models are expensive, time-consuming and can differ considerably from humans. It is accepted that the cancer microenvironment plays a critical role in the disease, thus, 3D models have been proposed as a potential solution to address the discrepancies of 2D and animal models. This review highlights changes in cell behaviour, including proliferation, gene expression and chemosensitivity, between cancer cells grown in 2D and 3D models for some of the most common cancers including lung, breast and prostate cancer as well as bone metastasis.
大多数评估癌症治疗方法的体外研究都是在二维（2D）单层中进行的，然后在体内动物模型中进行验证。然而，2D 模型无法准确模拟肿瘤微环境。此外，动物模型不能直接应用于模拟人类情况。三维（3D）培养模型可能有助于解决 2D 和动物模型的差异。当癌细胞逃离原发肿瘤时，它们可以侵入远处的器官，形成继发性肿瘤，称为转移。转移的发展导致患者的预期寿命显著下降。因此，也开发了用于模拟转移微环境的 3D 系统。多项研究表明，与 2D 相比，当细胞在 3D 中培养时，细胞行为和基因表达会发生变化，并得出与体内细胞更好的可比性的结论。特别重要的是，在响应抗癌治疗时观察到的效果，因为这些模型主要是作为药物测试平台构建的。本综述强调了在一些最常见的癌症（包括肺癌、乳腺癌和前列腺癌）中，在 2D 和 3D 模型中培养的癌细胞之间的这些变化。除了旨在模拟原发肿瘤部位的模型外，还描述了 3D 细胞培养在骨转移模型中的作用。
癌症研究中的大多数体外研究都是在 2D 中进行的，然后在体内动物模型中进行验证。然而，这两种模型都存在许多局限性：2D 模型无法准确模拟肿瘤微环境，而动物模型昂贵、耗时且与人类差异很大。人们普遍认为癌症微环境在疾病中起着至关重要的作用，因此，3D 模型已被提出作为解决 2D 和动物模型差异的潜在解决方案。本综述强调了在一些最常见的癌症（包括肺癌、乳腺癌和前列腺癌）中，2D 和 3D 模型中培养的癌细胞之间在细胞行为、包括增殖、基因表达和化学敏感性方面的变化，以及骨转移。
