Lee Minseok, Kim Seunggyu, Lee Sun Young, Son Jin Gyeong, Park Joonha, Park Seonghyeon, Yeun Jemin, Lee Tae Geol, Im Sung Gap, Jeon Jessie S
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, Daehak-ro 291, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daehak-ro 291, Yuseong-gu, Daejeon, 34141, Republic of Korea.
Bioact Mater. 2024 Jan 8;34:401-413. doi: 10.1016/j.bioactmat.2023.12.021. eCollection 2024 Apr.
vascularized cancer models utilizing microfluidics have emerged as a promising tool for mechanism study and drug screening. However, the lack of consideration and preparation methods for cancer cellular sources that are capable of adequately replicating the metastatic features of circulating tumor cells contributed to low relevancy with experimental results. Here, we show that the properties of cancer cellular sources have a considerable impact on the validity of the metastasis model. Notably, with a hydrophobic surface, we can create highly metastatic spheroids equipped with aggressive invasion, endothelium adhesion capabilities, and activated metabolic features. Combining these metastatic spheroids with the well-constructed microfluidic-based extravasation model, we validate that these metastatic spheroids exhibited a distinct extravasation response to epidermal growth factor (EGF) and normal human lung fibroblasts compared to the 2D cultured cancer cells, which is consistent with the previously reported results of experiments. Furthermore, the applicability of the developed model as a therapeutic screening platform for cancer extravasation is validated through profiling and inhibition of cytokines. We believe this model incorporating hydrophobic surface-cultured 3D cancer cells provides reliable experimental data in a clear and concise manner, bridging the gap between the conventional models and experiments.
利用微流体技术构建的血管化癌症模型已成为一种很有前景的机制研究和药物筛选工具。然而，由于缺乏能够充分复制循环肿瘤细胞转移特征的癌细胞来源的考虑因素和制备方法，导致实验结果的相关性较低。在这里，我们表明癌细胞来源的特性对转移模型的有效性有相当大的影响。值得注意的是，通过疏水表面，我们可以创建具有侵袭性、内皮细胞粘附能力和激活代谢特征的高转移性球体。将这些转移性球体与构建良好的基于微流体的外渗模型相结合，我们验证了与二维培养的癌细胞相比，这些转移性球体对表皮生长因子（EGF）和正常人肺成纤维细胞表现出明显的外渗反应，这与先前报道的实验结果一致。此外，通过对细胞因子的分析和抑制，验证了所开发模型作为癌症外渗治疗筛选平台的适用性。我们相信，这种包含疏水表面培养的三维癌细胞的模型以清晰简洁的方式提供了可靠的实验数据，弥合了传统模型与实验之间的差距。
