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Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids
Authors:Amy Y. Hsiao  Yu-suke Torisawa  Yi-Chung Tung  Sudha Sud  Russell S. Taichman  Kenneth J. Pienta  Shuichi Takayama
Affiliation:1. Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, United States;2. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan School of Medicine, Ann Arbor, MI, United States;3. Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States;4. Department of Urology, University of Michigan School of Medicine, Ann Arbor, MI, United States;5. Macromolecular Science and Engineering Program, University of Michigan College of Engineering, Ann Arbor, MI, United States;1. Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China;2. Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China;1. Department of Mechanical Engineering, MIT, Cambridge, MA, USA;2. Department of Biological Engineering, MIT, Cambridge, MA, USA;3. Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A-STAR), Biopolis, Singapore;1. Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China;2. The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province 646000, China;3. Department of Biology, Georgia Southern University, Statesboro, GA 30460, USA;4. Advanced Materials Lab, Polytechnic and Base Science School of University of Campania, San Lorenzo, 81031, Italy;1. Singapore-MIT Alliance for Research and Technology, BioSyM IRG, 1 Create Way, 138602, Singapore;2. DUKE-NUS Graduate Medical School Singapore, Emerging Infectious Disease Program, 8 College Road, 169857, Singapore;3. National University of Singapore, Department of Biochemistry, Yong Loo Lin School of Medicine MD7, 8 Medical Drive, 117597, Singapore;4. Massachusetts Institute of Technology, Department of Biological Engineering, 77 Massachusetts Avenue, 02139 Cambridge, MA, USA;1. University of Toronto, Institute of Biomaterials and Biomedical Engineering, 200 College St., Toronto, ON, M5S 3E5, Canada;2. University of Toronto, Department of Chemical Engineering and Applied Chemistry, 200 College St., Toronto, ON, M5S 3E5, Canada;3. Princess Margaret Cancer Centre, University Health Network, Canada
Abstract:The niche microenvironment in which cancer cells reside plays a prominent role in the growth of cancer. It is therefore imperative to mimic the in vivo tumor niche in vitro to better understand cancer and enhance development of therapeutics. Here, we engineer a 3D metastatic prostate cancer model that includes the types of surrounding cells in the bone microenvironment that the metastatic prostate cancer cells reside in. Specifically, we used a two-layer microfluidic system to culture 3D multi-cell type spheroids of fluorescently labeled metastatic prostate cancer cells (PC-3 cell line), osteoblasts and endothelial cells. This method ensures uniform incorporation of all co-culture cell types into each spheroid and keeps the spheroids stationary for easy tracking of individual spheroids and the PC-3's residing inside them over the course of at least a week. This culture system greatly decreased the proliferation rate of PC-3 cells without reducing viability and may more faithfully recapitulate the in vivo growth behavior of malignant cancer cells within the bone metastatic prostate cancer microenvironment.
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