Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
Biomimetic Model of Tumor Microenvironment on Microfluidic Platform
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DOI：
10.1002/adhm.201700196
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发表时间：
2017-08-09
影响因子：
10
通讯作者：
Jeon, Noo Li
中科院分区：
文献类型：
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作者：
Chung, Minhwan;Ahn, Jungho;Jeon, Noo Li
肿瘤微环境(TME)是肿瘤及其周围环境相互作用的复杂系统。TME最近引起了更多的关注，试图通过系统地了解癌症及其微环境来克服当前的耐药性和癌症的复发，而不是过去的简化论方法。然而，缺乏分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，提出了一种利用微流控平台的仿生TME模型，该模型能够全面地研究TME组分之间的相互作用。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显示出肿瘤细胞的显著形态变化，这取决于肿瘤细胞的类型，更重要的是，细胞外基质的组成。此外，该模型还允许直接观察肿瘤-间质相互作用所诱导的血管生成。最后，能够重建由肿瘤间质与TME模拟外部因素相互作用所诱导的同时的血管生成和淋巴管生成。相信所描述的体外仿生模型和实验概念将有助于阐明TME的复杂生物学。
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 tumorstromal 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.