A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells

// Jing Kong 1 , Yong Luo 2 , Dong Jin 1 , Fan An 2 , Wenyuan Zhang 1 , Lilu Liu 1 , Jiao Li 1 , Shimeng Fang 1 , Xiaojie Li 1 , Xuesong Yang 3 , Bingcheng Lin 2, 4 , Tingjiao Liu 1 1 College of Stomatology, Dalian Medical University, Dalian, China 2 Faculty of Chemical, Environmental and Biological Science and Technology, Dalian Technology University, Dalian, China 3 Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian, China 4 Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China Correspondence to: Tingjiao Liu, email: tingjiao@dlmedu.edu.cn Bingcheng Lin, email: bclin@dicp.ac.cn Keywords: microfluidic, metastasis, circulating tumor cells, multi-organ, bionic model Received: February 13, 2016      Accepted: April 02, 2016      Published: May 15, 2016 ABSTRACT A biomimetic microsystem might compensate costly and time-consuming animal metastatic models. Herein we developed a biomimetic microfluidic model to study cancer metastasis. Primary cells isolated from different organs were cultured on the microlfuidic model to represent individual organs. Breast and salivary gland cancer cells were driven to flow over primary cell culture chambers, mimicking dynamic adhesion of circulating tumor cells (CTCs) to endothelium in vivo . These flowing artificial CTCs showed different metastatic potentials to lung on the microfluidic model. The traditional nude mouse model of lung metastasis was performed to investigate the physiological similarity of the microfluidic model to animal models. It was found that the metastatic potential of different cancer cells assessed by the microfluidic model was in agreement with that assessed by the nude mouse model. Furthermore, it was demonstrated that the metastatic inhibitor AMD3100 inhibited lung metastasis effectively in both the microfluidic model and the nude mouse model. Then the microfluidic model was used to mimick liver and bone metastasis of CTCs and confirm the potential for research of multiple-organ metastasis. Thus, the metastasis of CTCs to different organs was reconstituted on the microfluidic model. It may expand the capabilities of traditional cell culture models, providing a low-cost, time-saving, and rapid alternative to animal models.