A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

Qihui Fan; Ruchuan Liu; Yang Jiao; Chunxiu Tian; James D. Farrell; Wenwen Diao; Xiaochen Wang; Fengrong Zhang; Wei Yuan; Haibo Han; Jinfeng Chen; Yue Yang; Xixiang Zhang; Fangfu Ye; Ming Li; Zhongcan Ouyang; Liyu Liu

doi:10.1039/C7LC00191F

A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions†

Qihui Fan,

^a Ruchuan Liu,^b Yang Jiao,^c Chunxiu Tian,^d James D. Farrell,^a Wenwen Diao,^e Xiaochen Wang,^a Fengrong Zhang,^a Wei Yuan,^f Haibo Han,^g Jinfeng Chen,^h Yue Yang,^h Xixiang Zhang,

^d Fangfu Ye,*^ai Ming Li,

^ai Zhongcan Ouyang*^ei and Liyu Liu*^b

Author affiliations

* Corresponding authors

^a Beijing National Laboratory for Condensed Matter Physics and CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
E-mail: fye@iphy.ac.cn

^b College of Physics, Chongqing University, Chongqing 401331, China
E-mail: lyliu@cqu.edu.cn

^c Materials Science and Engineering, Arizona State University, Tempe, Arizona, 85281 USA

^d Division of Physical Science and Engineering, King Abdullah University of Science & Technology, Thuwal, 23955-6900 Saudi Arabia

^e CAS Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China
E-mail: oy@itp.ac.cn

^f Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, Shenzhen University, Shenzhen, 518060 China

^g Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biobank, Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China

^h Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China

ⁱ School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

Abstract

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.

Lab on a Chip

A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions†

Abstract

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A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

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