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Issue 16, 2017
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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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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.

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

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Supplementary files

Article information


Submitted
24 Feb 2017
Accepted
04 Jul 2017
First published
10 Jul 2017

Lab Chip, 2017,17, 2852-2860
Article type
Paper

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

Q. Fan, R. Liu, Y. Jiao, C. Tian, J. D. Farrell, W. Diao, X. Wang, F. Zhang, W. Yuan, H. Han, J. Chen, Y. Yang, X. Zhang, F. Ye, M. Li, Z. Ouyang and L. Liu, Lab Chip, 2017, 17, 2852
DOI: 10.1039/C7LC00191F

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