The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate.
OBJECTIVE
Questions regarding the cell source and mechanisms in the initiation and progression of prostate cancer are today still open for debate. Indeed, our knowledge regarding prostate cell regulation, self-renewal, and cytodifferentiation is presently rather limited. In this study, we investigated these processes in the normal adult human prostate.


METHODS
Dynamic expression patterns in prostate stem/progenitor cells, intermediate/transit-amplifying cells, and cell lineages were immunohistochemically identified in an in situ explant renewal model of the human normal/benign adult prostate (n=6).


RESULTS
Cells with a basal phenotype proliferated significantly in explant cultures, whereas luminal cells went into apoptosis. Results further show down-regulation in tissue cultures of the basal and hypothetical stem cell marker Bcl-2 in the majority of cells, except in rare putative epithelial stem cells. Investigation of established (AC133) and novel candidate prostate stem/progenitor markers, including the cell surface receptor tyrosine kinase KIT and its ligand stem cell factor (SCF), showed that these rare epithelial cells are AC133(+)/CD133(low)/Bcl-2(high)/cytokeratin(+)/vimentin(-)/KIT(low)/SCF(low). In addition, we report on a stromal population that expresses the mesenchymal marker vimentin and that is AC133(-)/CD133(high)/Bcl-2(-)/cytokeratin(-)/KIT(high)/SCF(high).


CONCLUSIONS
We provide evidence for epithelial renewal in response to tissue culture and for basal and epithelial stem/progenitor cell recruitment leading to an expansion of an intermediate luminal precursor phenotype. Data further suggest that SCF regulates prostate epithelial stem/progenitor cells in an autocrine manner and that all or a subset of the identified novel stromal phenotype represents prostate stromal progenitor cells or interstitial pacemaker cells or both.
Ceder
Jens A
JA
Lund University, Department of Clinical Sciences, Division of Urological Research, University Hospital MAS, S-205 02 Malmö, Sweden. Jens.Ceder@med.lu.se
Jansson
Linda
L
Ehrnström
Roy A
RA
Rönnstrand
Lars
L
Abrahamsson
Per-Anders
PA
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000276:immunology; D012016:Reference Values; D019089:Stem Cell Factor / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D019089:Stem Cell Factor