Abstract 5023: A 3D perfusable platform for high-throughput screening diverse racial/ethnic prostate cancer specimens
Authors: Lindsey Sablatura, Kristin M. Bircsak, Mary C. Farach-Carson, Nora Navone, Peter Shepherd, Thomas Zarembinski, Pamela E. Constantinou, Anthony Saleh, Daniel A. Harrington
Journal: Cancer Research (2018)

Abstract Prostate cancer (PCa) incidence and mortality in African American men is more than 1.5 times greater than men of other races/ethnicities (i.e., Caucasian, Hispanic, American Indian/Alaska Native, Asian/Pacific Islander) in the United States. While elucidating the underlying mechanisms for this cancer health disparity is critical to patient treatment and improved patient outcome, currently, there are no in vitro models available to adequately recapitulate the PCa tumor microenvironment (TME) and aid in this effort. Advanced in vitro culture conditions, such as extended ex vivo culture of patient-derived xenografts (PDXs), 3-dimensional (3D) culture of cells within a defined extracellular matrix (ECM), miniaturization to formats compatible with high-throughput screening (HTS), controlled media perfusion, and co-culture of cancer, stroma, and endothelium, are key elements for improving PCa study, but few systems include two or more of these features. We have optimized culture conditions of a 3D in vitro model system, the OncoPlate, which mimics the PCa TME. In the OncoPlate, cells are seeded in engineered HyStem® hyaluronic acid (HA)-enriched hydrogels, optionally modified with migration-permissive peptides to mimic the tumor ECM. PDX-derived PCa cells are seeded in 3D in MIMETAS' microfluidic OrganoPlate® platform and co-cultured with stromal fibroblasts and endothelial blood vessel mimics under continuous perfusion. We predict that this engineered “tumor-on-a-chip” will better predict patient responses and, by incorporating PCa cells from patients with diverse racial backgrounds, support cancer health disparity research. Here we report culture of several PDX-derived PCa models of diverse racial origin cultured in our OncoPlate format. Live/dead staining followed by automated high content fluorescence imaging was utilized at various time points to characterize viability and growth rate of each model. Immunofluorescent staining for PSA (PCa cells), FSP (cancer associated fibroblasts), and VE-cadherin (endothelial cells) was used to display phenotype and health of each cell type in the culture over a week and formation of 3D structures characteristic of prostate cancer histology. Studies are ongoing to screen each model with a panel of chemotherapeutic drugs for which in vivo mouse PDX response data is available with the goal to improve predictive accuracy by using our perfusable OncoPlate PCa models. Citation Format: Lindsey Sablatura, Kristin M. Bircsak, Mary C. Farach-Carson, Nora Navone, Peter Shepherd, Thomas Zarembinski, Pamela E. Constantinou, Anthony Saleh, Daniel A. Harrington. A 3D perfusable platform for high-throughput screening diverse racial/ethnic prostate cancer specimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5023.