Trop2 identifies a subpopulation of murine and human prostate basal cells with stem cell characteristics

Abstract

The epithelium of the adult prostate contains 3 distinct cell types: basal, luminal, and neuroendocrine. Tissue-regenerative activity has been identified predominantly from the basal cells, isolated by expression of CD49f and stem cell antigen-1 (Sca-1). An important question for the field is whether all basal cells have stem cell characteristics. Prostate-specific microarray databases were interrogated to find candidate surface antigens that could subfractionate the basal cell population. Tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1/GA733-1) was identified because it was enriched after castration, in prostate sphere cells and in the basal fraction. In the murine prostate, Trop2 shows progenitor characteristics such as localization to the region of the gland proximal to the urethra and enrichment for sphere-forming and colony-forming cells. Trop2 subfractionates the basal cells into 2 populations, both of which express characteristic basal cell markers by quantitative PCR. However, only the basal cells expressing high levels of Trop2 were able to efficiently form spheres in vitro. In the human prostate, where Sca-1 is not expressed, sphere-forming progenitor cells were also isolated based on high expression of Trop2 and CD49f. Trop2-expressing murine basal cells could regenerate prostatic tubules in vivo, whereas the remaining basal cells had minimal activity. Evidence was found for basal, luminal, and neuroendocrine cells in prostatic tubules regenerated from Trop2 hi basal cells. In summary, functionally distinct populations of cells exist within the prostate basal compartment and an epithelial progenitor can give rise to neuroendocrine cells in vivo.neuroendocrine ͉ progenitor ͉ sphere assay

Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin

“…Rodent prostate basal epithelial cells are capable of adapting a luminal cell phenotype during in vitro culture (52). Several independent groups (19)(20)(21)(22)(23)(24)(25) have shown in a prostate regeneration assay that both human and rodent basal cells possess the capacity for multilineage differentiation. In the current study, we further showed that acute prostatic inflammation induced by bacterial infection significantly promoted basal-toluminal differentiation in situ.…”

“…Using a lineage-tracing approach, we and several other groups showed that adult murine prostate basal and luminal cell lineages are largely self-sustained when residing in their native microenvironment, although in two of the studies basal cells were shown to generate luminal cells at an extremely rare frequency (14)(15)(16)(17)(18). In stark contrast, other studies have shown that basal cells are able to differentiate very efficiently into luminal cells and neuroendocrine cells in a dissociated prostate-cell regeneration assay (19)(20)(21)(22)(23)(24)(25). In the prostate-cell regeneration assay, prostate basal epithelial cells were removed from their native environment, dissociated into single cells, and stimulated with embryonic urogenital sinus mesenchymal (UGSM) cells that have strong reprogramming activity (26)(27)(28).…”

Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium

“…Isolated and dissociated endometrial cells were plated in matrigel coated six-well plates and the number and type of colonies were scored after 8 d based on morphology and expression of epithelial vs. stromal markers. Trop2 is a cell surface marker expressed in uterine epithelium (10) (Fig. 2A).…”

Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages

“…The lineage relationship between basal and luminal cells has recently been under heavy debate. Although renal capsule or subcutaneous transplantation experiments support the traditional view that basal cells have the ability to regenerate the prostate gland by repopulating all prostate epithelial lineages [1][2][3][4] , evidence from the rescued explants of p63-null mice suggest that luminal cells can sustain a prostate structure independently of basal cells 5 . In addition, with transgenic reporter mice, a population of castration-resistant Nkx3.1-expressing luminal cells has been shown to be able to generate not only luminal cells but also other prostatic epithelial lineages 6 .…”