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一种新型微流控模型能够模拟循环肿瘤细胞的器官特异性转移。

A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells.

作者信息

Kong Jing, Luo Yong, Jin Dong, An Fan, Zhang Wenyuan, Liu Lilu, Li Jiao, Fang Shimeng, Li Xiaojie, Yang Xuesong, Lin Bingcheng, Liu Tingjiao

机构信息

College of Stomatology, Dalian Medical University, Dalian, China.

Faculty of Chemical, Environmental and Biological Science and Technology, Dalian Technology University, Dalian, China.

出版信息

Oncotarget. 2016 Nov 29;7(48):78421-78432. doi: 10.18632/oncotarget.9382.

Abstract

A biomimetic microsystem might compensate costly and time-consuming animal metastatic models. Herein we developed a biomimetic microfluidic model to study cancer metastasis. Primary cells isolated from different organs were cultured on the microlfuidic model to represent individual organs. Breast and salivary gland cancer cells were driven to flow over primary cell culture chambers, mimicking dynamic adhesion of circulating tumor cells (CTCs) to endothelium in vivo. These flowing artificial CTCs showed different metastatic potentials to lung on the microfluidic model. The traditional nude mouse model of lung metastasis was performed to investigate the physiological similarity of the microfluidic model to animal models. It was found that the metastatic potential of different cancer cells assessed by the microfluidic model was in agreement with that assessed by the nude mouse model. Furthermore, it was demonstrated that the metastatic inhibitor AMD3100 inhibited lung metastasis effectively in both the microfluidic model and the nude mouse model. Then the microfluidic model was used to mimick liver and bone metastasis of CTCs and confirm the potential for research of multiple-organ metastasis. Thus, the metastasis of CTCs to different organs was reconstituted on the microfluidic model. It may expand the capabilities of traditional cell culture models, providing a low-cost, time-saving, and rapid alternative to animal models.

摘要

一种仿生微系统可能会弥补成本高昂且耗时的动物转移模型的不足。在此,我们开发了一种仿生微流控模型来研究癌症转移。从不同器官分离出的原代细胞在微流控模型上培养,以代表各个器官。将乳腺癌和唾液腺癌细胞驱动流过原代细胞培养室,模拟循环肿瘤细胞(CTC)在体内与内皮细胞的动态黏附。这些流动的人工CTC在微流控模型上对肺显示出不同的转移潜能。采用传统的裸鼠肺转移模型来研究微流控模型与动物模型的生理相似性。结果发现,通过微流控模型评估的不同癌细胞的转移潜能与通过裸鼠模型评估的结果一致。此外,还证明了转移抑制剂AMD3100在微流控模型和裸鼠模型中均能有效抑制肺转移。然后,利用微流控模型模拟CTC的肝转移和骨转移,并证实了其用于多器官转移研究的潜力。因此,在微流控模型上重建了CTC向不同器官的转移。它可能会扩展传统细胞培养模型的能力,为动物模型提供一种低成本、省时且快速的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1097/5346650/45b301dbfa86/oncotarget-07-78421-g001.jpg

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