Graduate School at Shenzhen, Tsinghua University, Shenzhen, People's Republic of China.
Biofabrication. 2018 Jun 6;10(3):034102. doi: 10.1088/1758-5090/aac70c.
Tumour invasion into the surrounding stroma is a critical step in metastasis, and it is necessary to clarify the role of microenvironmental factors in tumour invasion. We present a microfluidic system that simulated and controlled multi-factors of the tumour microenvironment for three-dimensional (3D) assessment of tumour invasion into the stroma. The simultaneous, precise and continuous arrangement of two 3D matrices was visualised to observe the migration of cancer cell populations or single cells by transfecting cells with a fluorescent protein. A vascular endothelial layer was formed to simulate transendothelial transport of nutrients, and its endothelial barrier function was verified by the diffusion of 70 kDa fluorescein isothiocyanate (FITC)-Dextran in 3D matrices. Through high-throughput cell migration tracking observation and statistic evaluation, we clarified that cell density of the tumour directly determined its invasiveness. The results suggested that increased secretion of IL-6 among both cancer cells (MDA-MB-231) and noncancerous cells (MCF-10A or HDF-n) after co-culture contributes to cancer cell invasiveness, and this was verified by an IL-6 inhibitor assay. Finally, the drug efficacy of paclitaxel was reflected as changes in cancer cell migration ability, viability, and morphology. Together, our microfluidic devices could be a useful tool to study the mechanism of tumour invasion into the stroma and to screen anti-metastatic drugs.
肿瘤侵入周围基质是转移的关键步骤，有必要阐明微环境因素在肿瘤侵袭中的作用。我们提出了一种微流控系统，该系统模拟和控制了肿瘤微环境的多种因素，用于三维（3D）评估肿瘤侵入基质。通过转染带有荧光蛋白的细胞，可视化了两个 3D 基质的同时、精确和连续排列，以观察癌细胞群体或单个细胞的迁移。形成血管内皮层以模拟跨内皮运输营养物质，并且通过 70 kDa 异硫氰酸荧光素（FITC）-葡聚糖在 3D 基质中的扩散验证了其内皮屏障功能。通过高通量细胞迁移跟踪观察和统计评估，我们阐明了肿瘤的细胞密度直接决定其侵袭性。结果表明，共培养后癌细胞（MDA-MB-231）和非癌细胞（MCF-10A 或 HDF-n）之间 IL-6 的大量分泌有助于癌细胞的侵袭性，这通过 IL-6 抑制剂测定得到了验证。最后，紫杉醇的药物疗效反映为癌细胞迁移能力、活力和形态的变化。总之，我们的微流控装置可以成为研究肿瘤侵入基质的机制和筛选抗转移药物的有用工具。
