Neuroendocrine differentiation of human prostatic primary epithelial cells in vitro.
BACKGROUND
Dispersed prostatic neuroendocrine cells are involved in growth regulation of the prostate and are considered to play a role in the pathogenesis of prostate carcinoma and benign prostatic hyperplasia (BPH). They are meant either to be derived from the neural crest during embryogenesis or by direct differentiation of the cells from locally present precursor cells.


METHODS
An in vitro model was developed for human prostatic epithelial and neuroendocrine cell differentiation. Minced explants from radical prostatectomies were seeded on collagen I-coated plates.


RESULTS
The majority of outgrowing cells were basal cells, positive for cytokeratin markers K 5/14 and CD 44, as determined by confocal laser scanning microscopy. A small fraction of interdispersed single cells expressing c-kit, which is found on pluripotent precursors, was identified by immunofluorescence. From these basal cells, in vitro differentiation of cells with neuroendocrine morphology could be achieved within 3 days. These were at rest, i.e., non-bromodeoxyuridine incorporating cells and characteristically coexpressed K 5/14, K 18, and the neuroendocrine marker chromogranin A. Luminal cells staining for K 8 or 18 were not observed.


CONCLUSIONS
Neuroendocrine differentiation of adult prostatic cells was achieved in vitro, favoring the hypothesis that neuroendocrine cells are derived from peripheral precursor cells. The acceleration of this differentiation pathway may be the reason for the increased presence of neuroendocrine cells in areas of epithelial hyperplasia in BPH.
Rumpold
Holger
H
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Heinrich
Elmar
E
Untergasser
Gerold
G
Hermann
Martin
M
Pfister
Gerald
G
Plas
Eugen
E
Berger
Peter
P
D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D066298:In Vitro Techniques; D053555:Keratin-5; D007633:Keratins / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism
D053379:Chromogranin A; D002864:Chromogranins; D018960:Hyaluronan Receptors; C503940:KRT5 protein, human; D053555:Keratin-5; D012701:Serotonin; D007633:Keratins; D019009:Proto-Oncogene Proteins c-kit; D001973:Bromodeoxyuridine