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Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence

PURPOSE: 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 activ...

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Autores principales: Wagner, Jennifer, Damaschke, Nathan, Yang, Bing, Truong, Matthew, Guenther, Chad, McCormick, Johnathon, Huang, Wei, Jarrard, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398352/
https://www.ncbi.nlm.nih.gov/pubmed/25876105
http://dx.doi.org/10.1371/journal.pone.0124366
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author Wagner, Jennifer
Damaschke, Nathan
Yang, Bing
Truong, Matthew
Guenther, Chad
McCormick, Johnathon
Huang, Wei
Jarrard, David
author_facet Wagner, Jennifer
Damaschke, Nathan
Yang, Bing
Truong, Matthew
Guenther, Chad
McCormick, Johnathon
Huang, Wei
Jarrard, David
author_sort Wagner, Jennifer
collection PubMed
description PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. CONCLUSION: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.
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spelling pubmed-43983522015-04-21 Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence Wagner, Jennifer Damaschke, Nathan Yang, Bing Truong, Matthew Guenther, Chad McCormick, Johnathon Huang, Wei Jarrard, David PLoS One Research Article PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression. CONCLUSION: Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers. Public Library of Science 2015-04-15 /pmc/articles/PMC4398352/ /pubmed/25876105 http://dx.doi.org/10.1371/journal.pone.0124366 Text en © 2015 Wagner et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wagner, Jennifer
Damaschke, Nathan
Yang, Bing
Truong, Matthew
Guenther, Chad
McCormick, Johnathon
Huang, Wei
Jarrard, David
Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title_full Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title_fullStr Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title_full_unstemmed Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title_short Overexpression of the Novel Senescence Marker β-Galactosidase (GLB1) in Prostate Cancer Predicts Reduced PSA Recurrence
title_sort overexpression of the novel senescence marker β-galactosidase (glb1) in prostate cancer predicts reduced psa recurrence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398352/
https://www.ncbi.nlm.nih.gov/pubmed/25876105
http://dx.doi.org/10.1371/journal.pone.0124366
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