Department of Chemical Science and Technology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Department of Biotechnology and Biosciences, University of Milan-Bicocca, 20126 Milan, Italy.
Cells. 2024 Sep 13;13(18):1536. doi: 10.3390/cells13181536.
Developing accurate in vitro models that replicate the in vivo tumor environment is essential for advancing cancer research and therapeutic development. Traditional 2D cell cultures often fail to capture the complex structural and functional heterogeneity of tumors, limiting the translational relevance of findings. In contrast, 3D culture systems, such as spheroids, provide a more physiologically relevant context by replicating key aspects of the tumor microenvironment. This study aimed to compare the metabolism of three intrahepatic cholangiocarcinoma cell lines in 2D and 3D cultures to identify metabolic shifts associated with spheroid formation. Cells were cultured in 2D on adhesion plates and in 3D using ultra-low attachment plates. Metabolic exchange rates were measured using NMR, and intracellular metabolites were analyzed using LC-MS. Significant metabolic differences were observed between 2D and 3D cultures, with notable changes in central carbon and glutathione metabolism in 3D spheroids. The results suggest that 3D cultures, which more closely mimic the in vivo environment, may offer a more accurate platform for cancer research and drug testing.
开发能够复制体内肿瘤环境的精确体外模型对于推进癌症研究和治疗开发至关重要。传统的 2D 细胞培养往往无法捕捉肿瘤复杂的结构和功能异质性，限制了研究结果的转化相关性。相比之下，3D 培养系统，如球体，通过复制肿瘤微环境的关键方面，提供了更具生理相关性的环境。本研究旨在比较三种肝内胆管癌细胞系在 2D 和 3D 培养中的代谢情况，以鉴定与球体形成相关的代谢变化。细胞在附着平板上进行 2D 培养，在超低附着平板上进行 3D 培养。使用 NMR 测量代谢交换率，并使用 LC-MS 分析细胞内代谢物。在 2D 和 3D 培养之间观察到显著的代谢差异，3D 球体中中央碳和谷胱甘肽代谢发生了显著变化。结果表明，更接近体内环境的 3D 培养可能为癌症研究和药物测试提供更准确的平台。
