Progenitors in prostate development and disease

Abstract

The prostate develops by epithelial budding and branching processes that occur during fetal and postnatal stages. The adult prostate demonstrates remarkable regenerative capacity, with the ability to regrow to its original size over multiple cycles of castration and androgen administration. This capacity for controlled regeneration prompted the search for an androgen-independent epithelial progenitor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa). BPH is hypothesized to be a reawakening of ductal branching, resulting in the formation of new proximal glands, all while androgen levels are decreasing in the aging male. Advanced prostate cancer can be slowed with androgen deprivation, but resistance eventually occurs, suggesting the existence of an androgen-independent progenitor. Recent studies indicate that there are multiple castration-insensitive epithelial cell types in the proximal area of the prostate, but not all act as progenitors during prostate development or regeneration. This review highlights how recent cellular and anatomical studies are changing our perspective on the identity of the prostate progenitor.

Keywords: Androgen independent; Development; Lineage tracing; Morphogenesis; Progenitor; Prostate; Urethra.

Figure 1.

Establishment of proximal and distal compartments during prostate budding. The proximal luminal compartment is comprised of urethral luminal cells marked by KRT8 and KRT4 expression. The distal luminal compartment is comprised of KRT8 and NKX3-1 expressing luminal cells. The proximal and distal compartments are maintained separately during budding, branching, canalization, specification and differentiation. During androgen mediated regenerative growth after castration, the proximal and distal luminal lineages are largely self-sustaining. Under injury or inflammation, basal cells have been shown to reconstitute the luminal compartment.