Cells of Origin for Prostate Cancer.

Comprehensive knowledge of the normal prostate epithelial lineage hierarchy is a prerequisite to investigate the identity of the cells of origin for prostate cancer. The basal and luminal cells constitute most of the prostate epithelium and have been the major focuses of the study on the cells of origin for prostate cancer. Much progress has been made during the past few decades, mainly using mouse models, to understand the inter-lineage relationship and intra-lineage heterogeneity in adults as well as the lineage plasticity during conditions of stress. These studies have concluded that the adult mouse prostate basal and luminal cells are largely independently sustained under physiological conditions, but both types of cells possess the capacity for bipotent differentiation under stress or artificial experimental conditions. However, the existence or the identity of the putative progenitors within each lineage warrants further investigation. Whether the human prostate lineage hierarchy is completely the same as that of the mouse remains uncertain. Experiments from independent groups have demonstrated that both types of cells in mice and humans can serve as targets for transformation. But controversies remain whether the disease from distinct cells of origin display different clinical behaviors. Further investigation of the intra-lineage heterogeneity will provide new insights into this issue. Understanding the identity of the cells of origin for prostate cancer will help identify novel prognostic markers for early detection of aggressive prostate cancers, provide insights into the therapeutic vulnerability of these tumors, and inspire novel therapeutic strategies.