Biological gel-based microchamber array for tumor cell proliferation and migration studies in well-controlled biochemical gradients

• Published in: Lab on a chip 2021-08, Vol.21 (15), p.34-318
• Main Authors: Yao, Jingru, Li, Guoqiang, Jiao, Yang, Zheng, Yu, Liu, Yanping, Wang, Gao, Zhou, Lianjie, Zhang, Hongfei, Zhang, Xianquan, Shuai, Jianwei, Fan, Qihui, Ye, Fangfu, Lou, Silong, Chen, Guo, Song, Kena, Liao, Yong, Liu, Liyu
• Format: Article
• Language: English
• Subjects: Arrays; Biochips; Breast cancer; Chemical compounds; Epithelium; Growth factors; Inhibitors; Matrix metalloproteinases; Stability; Tumors
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/d0lc00951b

Breast cancer metastasis is a complex process controlled by multiple factors, including various cell-cell interactions, cell-environment coupling, and oxygen, nutrient and drug gradients that are intimately related to the heterogeneous breast tissue structure. In this study, we constructed a high-throughput in vitro biochip system containing an array of 642 microchambers arranged in a checkerboard configuration, with each chamber embedded in a composite extracellular matrix (ECM) composed of engineered collagen and Matrigel to mimic local heterogeneous environment in vivo . In addition, a controllable complex tetragonal chemical concentration profile can be achieved by imposing chemical compounds at the four boundaries of the chip, leading to distinct local nutrient and/or drug gradients in the individual microchambers. Here, the microchamber array with composite ECM (MACECM) device aims to simulate multiple tumor cell niches composed of both breast epithelial cells (MCF-10A-GFP) and metastatic breast cancer cells (MDA-MB-231-RFP), which enables systematic studies of cell responses to a variety of biochemical conditions. The results obtained from the MACECM studies indicate that discoidin domain receptor 1 (DDR1) inhibitor 7rh and matrix metalloproteinase inhibitor batimastat, in association with epidermal growth factor (EGF) had no significant effects on the growth of MCF-10A-GFP cells, but had significant effects on DDR1 expression and the related migratory behavior of MDA-MB-231-RFP cells. The MACECM design not only enables the construction of a more realistic in vitro model for investigating cancer cell migration mechanisms but also has considerable potential for further development as a platform for next-generation high-throughput and therapeutic screening ( e.g. , anti-cancer drug evaluation) and personalized medicine. A microchamber array with composite ECM device enables the construction of a more realistic model for investigating cancer migration mechanisms and has potential to serve as a platform for personalized medicine screening.