A bladder cancer microenvironment simulation system based on a microfluidic co-culture model
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Peng-fei Liu1,2,*, Yan-wei Cao1,3,*, Shu-dong Zhang4,*, Yang Zhao1,2, Xiao-guang Liu1,2, Hao-qing Shi1,2, Ke-yao Hu1,2, Guan-qun Zhu1,2, Bo Ma5 and Hai-tao Niu1,3
1 Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
2 The Medical College of Qingdao University, Qingdao, Shandong, China
3 Key Urology Laboratory of Qingdao City, Qingdao, Shandong, China
4 Department of Urology, Peking University Third Hospital, Beijing, China
5 Single Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China
* These authors have contributed equally to this work
Hai-tao Niu, email:
Bo Ma, email:
Keywords: microfluidic device, bladder cancer, microenvironment, three-dimensional culture, co-culture, drug sensitivity
Received: June 02, 2015 Accepted: September 26, 2015 Published: October 10, 2015
A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cells co-cultured simultaneously. This simulation system comprises perfusion equipment, matrigel channel units, a medium channel and four indirect contact culture chambers, allowing four types of cells to simultaneously interact through soluble biological factors and metabolites. With this system, bladder cancer cells (T24) with a tendency to form a ‘reticular’ structure under 3 dimensional culture conditions were observed in real time. The microenvironment characteristics of paracrine interactions and cell motility were successfully simulated in this system. The phenotype change process in stromal cells was successfully reproduced in this system by testing the macrophage effector molecule Arg-1. Arg-1 was highly expressed in the simulated tumor microenvironment group. To develop “precision medicine” in bladder cancer therapy, bladder cancer cells were treated with different clinical ‘neo-adjuvant’ chemotherapy schemes in this system, and their sensitivity differences were fully reflected. This work provides a preliminary foundation for neo-adjuvant chemotherapy in bladder cancer, a theoretical foundation for tumor microenvironment simulation and promotes individual therapy in bladder cancer patients.
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