Novel paired normal prostate and prostate cancer model cell systems 
derived from African American patients


 Prostate cancer is the most frequently diagnosed solid malignancy in men. African American (AA) men are at greater risk for developing prostate cancer, and experience higher mortality rates, as compared to Caucasian American (CA) men. However, mechanistic studies to understand this health disparity have been limited by the lack of relevant in vitro and in vivo models. There is an urgent need for preclinical cellular models to investigate molecular mechanisms underlying prostate cancer in AA men. We collected clinical specimens from radical prostatectomies of AA patients and established ten paired tumor-derived and normal epithelial cell cultures from the same donors, which were further cultivated to extend the growth under “conditional reprogramming (CR)”. Clinical and cellular annotations characterized these model cells as intermediate risk and predominantly diploid. Immunocytochemical analyses demonstrated variable expression levels of luminal (CK8) and basal (CK5, p63) markers in both normal and tumor cells. However, expression levels of TOPK, c-MYC, and N-MYC were markedly increased only in tumor cells. To determine cell utility for drug testing, we examined viability of cells following exposure to the anti-androgen (Bicalutamide) and two PARP-inhibitors (Olaparib and Niraparib) and observed decreased viability of tumor-derived cells as compared to viability of normal prostate derived cells.