Mechanical Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Institute of Advanced Machines and Design, Seoul National University, Seoul, 08826, Republic of Korea.
Adv Healthc Mater. 2017 Aug;6(15). doi: 10.1002/adhm.201700196. Epub 2017 May 24.
The "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in-depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner. Paracrine interactions of cocultured tumor cell lines (SK-OV-3, MKN-74, and SW620) with primary fibroblasts show marked morphological changes in the tumor cells, depending on the type of tumor cells, and, importantly, the composition of the extracellular matrix. Furthermore, this model allows direct observation of angiogenesis induced by the tumor-stroma interaction. Finally, reconstituting simultaneous angiogenesis and lymphangiogenesis induced by the tumor-stromal interaction with TME mimicking extrinsic factors is enabled. It is believed that the in vitro biomimetic model and the experimental concepts described will help to shed light on the complex biology of the TME.
“肿瘤微环境”（TME）是肿瘤及其周围环境之间复杂的相互作用系统。最近，人们越来越关注 TME，试图通过系统地了解癌症及其微环境，超越过去的还原论方法，克服当前的耐药性和癌症复发问题。然而，缺乏用于剖析复杂相互作用的实验工具，阻碍了对 TME 的深入研究。在这里，我们提出了一种使用微流控平台的仿生 TME 模型，该模型能够全面研究 TME 成分之间的相互作用。共培养的肿瘤细胞系（SK-OV-3、MKN-74 和 SW620）与原代成纤维细胞的旁分泌相互作用，根据肿瘤细胞的类型，以及重要的是细胞外基质的组成，导致肿瘤细胞发生明显的形态变化。此外，该模型还可以直接观察到肿瘤-基质相互作用诱导的血管生成。最后，通过模拟外在因素，实现了肿瘤-基质相互作用诱导的血管生成和淋巴管生成的同时重建。我们相信，这种体外仿生模型和所描述的实验概念将有助于揭示 TME 的复杂生物学。
