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

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2852-2860
Number of pages9
JournalLab on a Chip
Volume17
Issue number16
DOIs
StatePublished - 2017

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ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Biochemistry
  • Biomedical Engineering

Cite this

Fan, Q., Liu, R., Jiao, Y., Tian, C., Farrell, J. D., Diao, W., Wang, X., Zhang, F., Yuan, W., Han, H., Chen, J., Yang, Y., Zhang, X., Ye, F., Li, M., Ouyang, Z., & Liu, L. (2017). A novel 3-D bio-microfluidic system mimicking: In vivo heterogeneous tumour microstructures reveals complex tumour-stroma interactions. Lab on a Chip, 17(16), 2852-2860. https://doi.org/10.1039/c7lc00191f