Department of Histopathology, Trinity College Dublin, Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland.
Trinity St James's Cancer Institute, Dublin 8, Ireland.
Sci Rep. 2023 Mar 6;13(1):3704. doi: 10.1038/s41598-023-30733-6.
Circulating tumour cells (CTCs) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha (HIF-1α). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.
循环肿瘤细胞 (CTC) 是癌症转移过程中的关键中间步骤。CTC 分离/纯化的可靠性限制了转移性进展的报告潜力，也限制了 CTC 作为治疗干预靶点的发展。在这里，我们报告了一种新的方法，该方法使用原发性癌细胞作为模型系统来优化 CTC 的培养条件。我们利用了 CTC 在缺氧条件下茁壮成长的已知生物学特性，其存活和增殖依赖于缺氧诱导因子 1α（HIF-1α）的激活。我们从癌症患者的血液中分离出上皮样和拟间充质 CTC 表型，并成功地将这些细胞培养了 8 周以上。需要 CTC 簇的存在才能建立和维持长期培养。这种用于 CTC 长期培养的新方法将有助于下游应用的发展，包括 CTC 治疗学。
