Overexpression of the novel senescence marker β-galactosidase (GLB1) in prostate cancer predicts reduced PSA recurrence

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124366-e0124366
• Main Authors: Wagner, Jennifer, Damaschke, Nathan, Yang, Bing, Truong, Matthew, Guenther, Chad, McCormick, Johnathon, Huang, Wei, Jarrard, David
• Format: Article
• Language: English
• Subjects: Aged; Aging; Antineoplastic Agents - pharmacology; Aziridines - pharmacology; Benzoquinones - pharmacology; beta-Galactosidase - genetics; beta-Galactosidase - metabolism; Biomarkers - metabolism; Cancer; Cellular Senescence - drug effects; Chemotherapy; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Experimental design; Formaldehyde; Galactose; Galactosidase; Gene Expression Regulation, Neoplastic; Glycoconjugates; Humans; Kallikreins - genetics; Kallikreins - metabolism; Male; Metastases; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Paraffin; Paraffin Embedding; Primary Cell Culture; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostate-Specific Antigen - genetics; Prostate-Specific Antigen - metabolism; Prostatic intraepithelial neoplasia; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Senescence; Signal Transduction; Survival; Survival Analysis; Tissue Fixation; Tissues; Tumor suppressor genes; Tumors; β-Galactosidase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124366

Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1) hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues. In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series. GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p