Physiological hypoxia promotes cancer cell migration and attenuates angiogenesis in co-culture using a microfluidic device

IF 2.3 4区 工程技术 Q2 INSTRUMENTS & INSTRUMENTATION
Satoshi Aratake, Kenichi Funamoto
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引用次数: 0

Abstract

In the tumor microenvironment (TME), the interaction between cancer cells and the microvascular network plays a crucial role in cancer progression. It is also well known that an extremely low oxygen concentration is generated in the TME. However, the effects of oxygen concentration on the interaction between cancer cells and the microvascular network remain poorly understood. In the present study, we developed a microfluidic device with three gel channels and used this device to co-culture cancer cells and a microvascular network. We then investigated the cellular dynamics at different oxygen concentrations. Cancer cells and cells forming a microvascular network (endothelial cells and fibroblasts) were separately mixed with fibrin gels and placed in separate gel channels that flanked a middle gel channel lacking cells. During a seven-day co-culture, the dynamics of cancer cells and formation of a three-dimensional microvascular structure were observed. Cell culture was conducted at three different oxygen concentrations: atmospheric oxygen (21% O2), physiological normoxia (5% O2), and physiological hypoxia (1% O2, resembling the TME). Inspection revealed that cancer cells migrated toward the microvascular network under the co-culture conditions, a property that was potentiated at lower oxygen levels. Under physiological normoxia, endothelial cells formed a thick, dense microvascular network rather than migrating towards the cancer cells. In contrast, under physiological hypoxia, endothelial cells did not exhibit angiogenesis toward cancer cells. These results suggest that the microfluidic device described here will be useful for investigating the interactions between cancer cells and microvascular network under various oxygen conditions.

利用微流体设备在共培养过程中,生理性缺氧可促进癌细胞迁移并抑制血管生成
在肿瘤微环境(TME)中,癌细胞与微血管网络之间的相互作用对癌症的发展起着至关重要的作用。众所周知,肿瘤微环境中的氧气浓度极低。然而,人们对氧浓度对癌细胞与微血管网络之间相互作用的影响仍然知之甚少。在本研究中,我们开发了一种带有三个凝胶通道的微流控装置,并利用该装置共同培养癌细胞和微血管网络。然后,我们研究了不同氧气浓度下的细胞动态。癌细胞和形成微血管网络的细胞(内皮细胞和成纤维细胞)分别与纤维蛋白凝胶混合,并分别置于不同的凝胶通道中,中间的凝胶通道两侧没有细胞。在为期七天的共培养过程中,观察了癌细胞的动态和三维微血管结构的形成。细胞培养在三种不同的氧气浓度下进行:大气氧(21% O2)、生理性常氧(5% O2)和生理性缺氧(1% O2,类似于 TME)。检查发现,在共培养条件下,癌细胞向微血管网络迁移,这一特性在较低氧水平下得到加强。在生理性常氧条件下,内皮细胞形成了厚而密集的微血管网络,而不是向癌细胞迁移。相反,在生理性缺氧条件下,内皮细胞并不表现出向癌细胞的血管生成。这些结果表明,本文所述的微流控装置将有助于研究各种氧气条件下癌细胞与微血管网络之间的相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microfluidics and Nanofluidics
Microfluidics and Nanofluidics 工程技术-纳米科技
CiteScore
4.80
自引率
3.60%
发文量
97
审稿时长
2 months
期刊介绍: Microfluidics and Nanofluidics is an international peer-reviewed journal that aims to publish papers in all aspects of microfluidics, nanofluidics and lab-on-a-chip science and technology. The objectives of the journal are to (1) provide an overview of the current state of the research and development in microfluidics, nanofluidics and lab-on-a-chip devices, (2) improve the fundamental understanding of microfluidic and nanofluidic phenomena, and (3) discuss applications of microfluidics, nanofluidics and lab-on-a-chip devices. Topics covered in this journal include: 1.000 Fundamental principles of micro- and nanoscale phenomena like, flow, mass transport and reactions 3.000 Theoretical models and numerical simulation with experimental and/or analytical proof 4.000 Novel measurement & characterization technologies 5.000 Devices (actuators and sensors) 6.000 New unit-operations for dedicated microfluidic platforms 7.000 Lab-on-a-Chip applications 8.000 Microfabrication technologies and materials Please note, Microfluidics and Nanofluidics does not publish manuscripts studying pure microscale heat transfer since there are many journals that cover this field of research (Journal of Heat Transfer, Journal of Heat and Mass Transfer, Journal of Heat and Fluid Flow, etc.).
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