A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions
Farrell, James D.
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
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AbstractA 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.
CitationFan Q, Liu R, Jiao Y, Tian C, Farrell JD, et al. (2017) A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions. Lab Chip 17: 2852–2860. Available: http://dx.doi.org/10.1039/c7lc00191f.
SponsorsWe thank Prof. Robert H. Austin in the Physics Department, Princeton University for stimulating discussions. This work was supported by the State Key Development Program for Basic Research of China (Grant No. 2013CB837200, No. 2013CB932803), the China Postdoctoral Science Foundation funded project (Grant No. 2016M591275), the Chinese Academy of Sciences, the Key Research Program of Frontier Sciences CAS (Grant No. QYZDJ-SSW-SYS014 and QYZDB-SSW-SYS003), the National Natural Science Foundation of China (Grant No. 11474345, No. 11674043, No. 11574382, the joint NSFC-ISF Research Program with Grant No. 51561145002), and Arizona State University start-up funds.
PublisherRoyal Society of Chemistry (RSC)
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