Developing a Novel Two-Dimensional Culture System to Enrich Human Prostate Luminal Progenitors That Can Function as a Cell of Origin for Prostate Cancer.

摘要: Elucidating the cell of origin cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells normal human prostate (NHP) can function as (PCa). Here, we show organoids derived from bulk NHP luminal also be tumorigenically transformed. We further WIT medium, which is used to culture mammary epithelial progenitor cells, when combined with ROCK inhibitor, readily propagate a population progenitor-like primary isolates. Such functionally defined progenitors transformed by distinct sets genetic perturbations (i.e., AR+AKT/ERG or c-MYC+PTEN knockout) form tumor glands. Genome-wide RNA-Seq analysis freshly purified unperturbed benign prostatic culture-expanded lineage-specific stem/progenitor populations reveals possess gene expression profile greatly enriched advanced, castration-resistant, metastatic PCa, it associates poor patient survival. The ability simple two-dimensional system reported herein enrich should facilitate biological biochemical well high-throughput screening these PCa cells. Stem Cells Translational Medicine 2017;6:748-760.