Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip.
Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip.
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模拟血管微环境微流控芯片上肿瘤细胞行为的研究
DOI：
10.1038/srep17768
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发表时间：
2015-12-03
影响因子：
4.6
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Huang R;Zheng W;Liu W;Zhang W;Long Y;Jiang X
肿瘤细胞的外渗是肿瘤转移的关键事件。然而，肿瘤细胞外渗的潜在机制仍然未知，主要受到传统细胞培养中生物组织缺乏复杂性以及体内实验的昂贵和伦理问题的阻碍。因此，需要一种廉价、省时省力、最重要的是血管微环境模拟研究模型。在此，我们报告了一种基于微流控芯片的肿瘤外渗研究模型，该模型能够同时模拟人体血管系统的机械和生物化学微环境，并分析它们对肿瘤外渗的协同作用。在血管系统的不同力学条件下，肿瘤细胞（HeLa细胞）在毛细血管微环境中具有最高的存活率和粘附活性。肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）在血流动力学背景下破坏了内皮细胞单层的完整性，促进了肿瘤细胞的粘附，而铂纳米粒（platinum nanoparticles，Pt-NPs）可使这种情况得到恢复。该模型弥补了细胞培养和动物实验之间的差距，是研究肿瘤在血管系统中行为的一个有前途的平台。
The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system.