Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression

Abstract

Prostate cancer is a leading cause of cancer-related death in adult men. It can regress dramatically upon antihormonal therapy, but it often recurs in a more aggressive, androgen-independent form. Defining the prostate tissue stem cells (PrSCs) and their involvement in cancer initiation and maintenance may lead to better therapeutics. Using a tissue-regeneration model in which dissociated prostate epithelial cells mixed with inductive mesenchyme give rise to prostatic tubules, we have identified a small population of prostate cells that contains multiple stem cell characteristics. In this system, prostate cancer can be initiated by autocrine or paracrine growth factor signaling and intracellular overexpression of genes often found mutated in human prostate cancer. Using an in vitro prostate sphere assay, we further defined the PrSC population and demonstrated their selfrenewal and multilineage differentiation capabilities. Microarray analyses of the stem-and non-stem-cell populations have assisted us in finding and evaluating additional markers that can better define the PrSC population and further delineate the different cell types of the prostate, including those that serve as the target cell for tumor initiation.

Prostate Cancer Cell Lines under Hypoxia Exhibit Greater Stem-Like Properties

“…Furthermore, the colony efficiency of the CD44 bright cells was significantly improved following hypoxic pretreatment, whereas the CD44 dim cells did not respond to such hypoxic exposure. Since colony formation and sphere formation capabilities are confined to stem cells [46], [55], [56], these results may support the hypothesis that CD44 bright cells possess stem-like properties in the prostate cancer cells [54].…”

DNA methylation of E-cadherin is a priming mechanism for prostate development

“…CD49f (also known as integrin alpha 6, Itga6 ) marks mature prostate basal epithelium (Lukacs et al, 2008; Lukacs et al, 2010; Lawson et al, 2007) and we confirmed it also marks fetal prostate basal epithelium within the urethra and developing prostate buds (Fig. 2C, inset).…”

Isolation, cultivation and characterization of adult murine prostate stem cells

“…Epithelial cells quickly lose their self-renewal potential when they are cultured in two-dimensions15. We have developed a three-dimensional culture system to maintain and expand primitive prostate cells that retain the capacity for both self-renewal and differentiation14.…”

“…Similar to other epithelial stem cell assays, the colony-forming assay is performed in a two-dimensional culture system and measures both proliferative colony-forming activity and differentiation. Colonies are clonal in origin, express basal and luminal keratins, and can be induced to undergo differentiation upon addition of androgen10,14,15. The sphere-forming assay is performed under three-dimensional conditions, as described above.…”