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STEM CELL FEATURES OF BENIGN AND MALIGNANT PROSTATE EPITHELIAL CELLS

1998; Lippincott Williams & Wilkins; Volume: 160; Issue: 6 Part 2 Linguagem: Inglês

10.1016/s0022-5347(01)62196-7

1527-3792

Angelo M. De Marzo, William G. Nelson, Alan K. Meeker, Donald S. Coffey,

Immunotherapy and Immune Responses

No AccessJournal of UrologyFestschrift in Honor of 85th Birthday of Dr. William Wallace Scott, Sr1 Dec 1998STEM CELL FEATURES OF BENIGN AND MALIGNANT PROSTATE EPITHELIAL CELLS ANGELO M. DE MARZO, WILLIAM G. NELSON, ALAN K. MEEKER, and DONALD S. COFFEY ANGELO M. DE MARZOANGELO M. DE MARZO , WILLIAM G. NELSONWILLIAM G. NELSON , ALAN K. MEEKERALAN K. MEEKER , and DONALD S. COFFEYDONALD S. COFFEY View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62196-7AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We present a new hypothesis suggesting that the different malignant potential of benign prostatic hyperplasia (BPH) and high grade prostatic intraepithelial neoplasia may be explained by distinct alterations in stem cell-like properties. Materials and Methods: We used our results and the recent literature to developed this hypothesis in the context of an updated prostate stem cell model. Results: While high grade prostatic intraepithelial neoplasia is a likely precursor lesion to many prostatic adenocarcinomas, BPH rarely if ever progresses directly to carcinoma. Prostate epithelium contains basal and secretory compartments. Secretory cells appear to differentiate from basal cells. Thus, prostatic stem cells most likely reside in the basal compartment. In BPH there is a slight increase in epithelial proliferation, yet most replicating epithelial cells within BPH maintain their normal restriction to the basal compartment. In high grade prostatic intraepithelial neoplasia there is a marked increase in cell proliferation. In contrast to BPH, the majority of proliferating cells in high grade prostatic intraepithelial neoplasia reside in the secretory compartment. The biological significance of this topographic infidelity of proliferation in high grade prostatic intraepithelial neoplasia remains unclear but may relate mechanistically to down regulation of the cyclin dependent kinase inhibitor, p27kip1. Normal basal cells express GSTP1, an enzyme that inactivates reactive electrophiles and organic hydroperoxides, and that may protect cells from deoxyribonucleic acid damaging agents. In contrast, normal secretory cells and high grade prostatic intraepithelial neoplasia cells do not express this enzyme. Conclusions: We propose that topographic infidelity of proliferation produces a population of secretory cells replicating in the absence of key genome protective mechanisms, thus setting the stage for an accumulation of genomic alterations and instability in high grade prostatic intraepithelial neoplasia. This action occurs along with activation of telomerase, resulting in an immortal clone capable of developing into invasive carcinoma. 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Google Scholar From the Department of Pathology, James Buchanan Brady Urological Institute and The Johns Hopkins Oncology Center, The Johns Hopkins University Medical Institutions, Baltimore, MarylandSupported by Public Health Services Grant DK22000-25 and the National Cancer Institute Special Program in Research Excellence Grant P50 CA-58236.© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 160Issue 6 Part 2December 1998Page: 2381-2392 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.Keywordsprostatic neoplasmsstem cellsprostatic hypertrophytransferasescyclinsMetricsAuthor Information ANGELO M. DE MARZO More articles by this author WILLIAM G. NELSON More articles by this author ALAN K. MEEKER More articles by this author DONALD S. COFFEY More articles by this author Expand All Advertisement PDF downloadLoading ...