Identification of a stem cell candidate in the normal human prostate gland.
Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus. In adult normal prostate tissue, the average abundance of Ck6a+ cells was 4.9%. With proliferative stimuli in the prostate organ culture model, in which the epithelial-stromal interaction was maintained, a remarkable increase of Ck6a expression was noticed to up to 64.9%. The difference in cytokeratin 6a expression between the normal adult prostate and the prostate organ culture model was statistically significant (p<0.0001). Within the prostate organ culture model the increase of cytokeratin 6a-expressing cells significantly correlated with increased proliferation index (r = 0.7616, p = 0.0467). The Ck6a+ cells were capable of differentiation as indicated by their expression of luminal cell markers such as ZO-1 and prostate specific antigen (PSA). Our data indicate that Ck6a+ cells represent a prostatic epithelial stem cell candidate possessing high potential for proliferation and differentiation. Since the development of benign prostatic hyperplasia and prostate carcinogenesis are disorders of proliferation and differentiation, the Ck6a+ cells may represent a major element in the development of these diseases.
Schmelz
Monika
M
Department of Pathology, Southern Arizona Veterans Affairs Health Care System, 3601 S. 6th Ave., Tucson, AZ 85723, USA. monika.schmelz@med.va.gov
Moll
Roland
R
Hesse
Ulrike
U
Prasad
Anil R
AR
Gandolfi
Jay A
JA
Hasan
Shirin R
SR
Bartholdi
Marty
M
Cress
Anne E
AE
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007633:Keratins