Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

Abstract

We previously showed that prostatic stem cells are concentrated in the proximal regions of prostatic ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of ducts was more effective in generating prostatic tissue than a comparable population of Sca-1-depleted cells (203.0 ؎ 83.1 mg vs. 11.9 ؎ 9.2 mg) or a population of Sca-1-expressing cells isolated from the remaining regions of ducts (transit-amplifying cells) (31.9 ؎ 24.1 mg). Almost all of the proliferative capacity of the proximal duct Sca-1-expressing cell population resides within the fraction of cells that express high levels of Sca-1 (top one-third), with the proximal region of prostatic ducts containing 7.2-fold more Sca-1 high cells than the remaining regions. More than 60% of the high-expressing cells coexpress ␣6 integrin and the antiapoptotic factor Bcl-2, markers that are also characteristic of stem cells of other origins. Further stratification of the phenotype of the stem cells may enable the development of rational therapies for treating prostate cancer and benign prostatic hyperplasia.prostate ͉ ␣6 integrin ͉ Bcl-2

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

“…cells from the proximal region had even higher regenerative activity than the Sca-1-positive cells from the intermediate and distal regions (Burger et al 2005). Using 7AAD-staining, DNA-staining, and pyronin-Y RNAstaining techniques, we have shown that the Sca-1-positive cell fraction is enriched for quiescent cells, as defined by low RNA and DNA staining (Xin et al 2005).…”

“…Since then, populations enriched for stem cell activity have been isolated from many adult tissues using various magnetic bead and FACS techniques Stingl et al 2006;Corti et al 2007). We and other investigators first identified the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 as a marker that can enrich for prostate stem cell activity, using magnetic bead sorting methods combined with in vitro and in vivo readout assays (Burger et al 2005;Xin et al 2005). …”

“…The three independent lists of genes had only one in common: integrin α 6 , also known as CD49f. A fraction of Sca-1-positive cells in the prostate express the stem cell markers CD49f and Bcl-2 (Burger et al 2005;Lawson et al 2007). Immunofluorescence analysis revealed that CD49f is strictly located on the basal surface of basal cells in the mouse prostate.…”

Vascular density is highest in the proximal region of the mouse prostate

“…This region has been identified as the site of the organ's repository of epithelial stem cells (4,5,23). As stem cells lie in a special niche that nourishes them and keeps them in a primitive state, the high vascularity may contribute to the formation of the niche.…”

Prostate cancer stem cell therapy: hype or hope?

“…Evidence has been published for normal prostate epithelial stem or progenitor cells in the human [18][19][20] and mouse prostate. [21][22][23][24][25] Mouse data suggest that the stem cell compartment lies towards the base of the ducts near where they join the urethra. [26][27][28] Prostate tissue can be reconstituted by embryonic stem cells.…”