Human prostate sphere‐forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo

Abstract

BACKGROUNDProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.METHODSProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.RESULTSProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3–5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5–4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8−AR−PSA−) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.CONCLUSIONHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells. Prostate 70: 491–501, 2010. © 2009 Wiley-Liss, Inc.

β4 Integrin signaling induces expansion of prostate tumor progenitors

“…Furthermore, the expression of ErbB3 was restricted to LNCaP and DU145 cells ( Figure 6A). Interestingly, the normal prostate epithelial cells, PrEC cells, which possess a phenotype similar to basal-like transit-amplifying cells (53,54), were found to express high levels of β4 and a repertoire of RTKs similar to those of androgen-independent prostate carcinoma cell lines ( Figure 6A).…”

JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells

“…Cancer stem cells have been isolated from a wide range of cancers including leukemia (21), breast (22), brain (23,24), lung (25), colon (26), pancreas (27), and prostate (28 (29,30), and CD44 þ CD49f hi Trop2 þ (31) have many of the properties of cancer stem cells. Gene expression profiling of CD44 þ /a 2 b 1 hi /CD133 þ cancer cells, from primary cultures, revealed significant over-representation of several components of the JAK-STAT signaling pathway (32) providing further evidence of the role of this signaling pathway in prostate cancer.…”

Evaluation ofalpha-methylacyl-CoA racemase, metallothionein and prostate specific antigen as prostate cancer prognostic markers

“…It represents one of the most frequent cancers in developed countries and common cause of cancer-related death [1,2]. Recently significantly increased number of newly diagnosed patients suffering from this malignant disease is directly related to introduction of prostatic specific antigen (PSA) evaluation to the clinical practice [3][4][5][6][7]. This marker enabled detection of early stages of disease, undetectable when commonly used rectal investigation is employed.…”