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Characterization and clinical relevance of ALDHbright populations in prostate cancer

Le Magnen, C. and Bubendorf, L. and Rentsch, C. A. and Mengus, C. and Gsponer, J. and Zellweger, T. and Rieken, M. and Thalmann, G. N. and Cecchini, M. G. and Germann, M. and Bachmann, A. and Wyler, S. and Heberer, M. and Spagnoli, G. C.. (2013) Characterization and clinical relevance of ALDHbright populations in prostate cancer. Clinical cancer research, Vol. 19, no. 19. pp. 5361-5371.

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Official URL: http://edoc.unibas.ch/dok/A6338105

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Abstract

PURPOSE: High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDH(bright)) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDH(bright) populations in clinical prostate cancer specimens. EXPERIMENTAL DESIGN: We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDH(bright) populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer. RESULTS: ALDH(bright) cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P > 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naive patients. CONCLUSIONS: Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Chirurgische Forschung (Heberer)
UniBasel Contributors:Spagnoli, Giulio C. and Heberer, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Association for Cancer Research
ISSN:1078-0432
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2015 07:44
Deposited On:06 Mar 2015 07:44

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