Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer


Autoria(s): Le Magnen, Clémentine; Bubendorf, Lukas; Rentsch, Cyrill A.; Mengus, Chantal; Gsponer, Joel; Zellweger, Tobias; Rieken, Malte; Thalmann, George N.; Cecchini, Marco G.; Germann, Markus; Bachmann, Alexander; Wyler, Stephen; Heberer, Michael; Spagnoli, Giulio C.
Data(s)

2013

Resumo

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-naïve patients. CONCLUSIONS Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.

Formato

application/pdf

Identificador

http://boris.unibe.ch/43750/1/Thalmann_Clin%20Cancer%20Res_2013_19_5361.pdf

Le Magnen, Clémentine; Bubendorf, Lukas; Rentsch, Cyrill A.; Mengus, Chantal; Gsponer, Joel; Zellweger, Tobias; Rieken, Malte; Thalmann, George N.; Cecchini, Marco G.; Germann, Markus; Bachmann, Alexander; Wyler, Stephen; Heberer, Michael; Spagnoli, Giulio C. (2013). Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer. Clinical cancer research, 19(19), pp. 5361-5371. Association for Cancer Research 10.1158/1078-0432.CCR-12-2857 <http://dx.doi.org/10.1158/1078-0432.CCR-12-2857>

doi:10.7892/boris.43750

info:doi:10.1158/1078-0432.CCR-12-2857

info:pmid:23969936

urn:issn:1078-0432

Idioma(s)

eng

Publicador

Association for Cancer Research

Relação

http://boris.unibe.ch/43750/

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Le Magnen, Clémentine; Bubendorf, Lukas; Rentsch, Cyrill A.; Mengus, Chantal; Gsponer, Joel; Zellweger, Tobias; Rieken, Malte; Thalmann, George N.; Cecchini, Marco G.; Germann, Markus; Bachmann, Alexander; Wyler, Stephen; Heberer, Michael; Spagnoli, Giulio C. (2013). Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer. Clinical cancer research, 19(19), pp. 5361-5371. Association for Cancer Research 10.1158/1078-0432.CCR-12-2857 <http://dx.doi.org/10.1158/1078-0432.CCR-12-2857>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed