title: A bladder cancer microenvironment simulation system based on a microfluidic co-culture model.
abstract: 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.
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Peng-fei
authors.initials: PF
authors.lastname: Liu
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|Key Urology Laboratory of Qingdao City, Qingdao, Shandong, China.
authors.forename: Yan-wei
authors.initials: YW
authors.lastname: Cao
authors.affiliation: Department of Urology, Peking University Third Hospital, Beijing, China.
authors.forename: Shu-dong
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Xiao-guang
authors.initials: XG
authors.lastname: Liu
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Hao-qing
authors.initials: HQ
authors.lastname: Shi
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Ke-yao
authors.initials: KY
authors.lastname: Hu
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|The Medical College of Qingdao University, Qingdao, Shandong, China.
authors.forename: Guan-qun
authors.initials: GQ
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.|Key Urology Laboratory of Qingdao City, Qingdao, Shandong, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Niu
mesh_terms: D000970:Antineoplastic Agents; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D044085:Microfluidics / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents
keywords: bladder cancer; co-culture; drug sensitivity; microenvironment; microfluidic device; three-dimensional culture