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Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate
Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946793/ https://www.ncbi.nlm.nih.gov/pubmed/24296879 http://dx.doi.org/10.1038/labinvest.2013.141 |
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author | Maund, Sophia L. Nolley, Rosalie Peehl, Donna M. |
author_facet | Maund, Sophia L. Nolley, Rosalie Peehl, Donna M. |
author_sort | Maund, Sophia L. |
collection | PubMed |
description | Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro and in vivo models. “Tissue slice cultures” (TSC) provide realistic preclinical models of diverse tissues and organs, but have not been fully developed or widely utilized for prostate studies. Problems encountered include degeneration of differentiated secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we optimized, characterized, and applied a TSC model of primary human PCa and benign prostate tissue that overcomes many deficiencies of current in vitro models. Tissue cores from fresh prostatectomy specimens were precision-cut at 300-µm and incubated in a rotary culture apparatus. The ability of varied culture conditions to faithfully maintain benign and cancer cell and tissue structure and function over time was evaluated by immunohistological and biochemical assays. After optimization of the culture system, molecular and cellular responses to androgen ablation and to piperlongumine, purported to specifically reduce androgen signaling in PCa, were investigated. Optimized culture conditions successfully maintained the structural and functional fidelity of both benign and PCa TSCs for 5 days. TSCs exhibited androgen-dependence, appropriately undergoing ductal degeneration, reduced proliferation, and decreased prostate-specific antigen expression upon androgen ablation. Furthermore, TSCs revealed cancer-specific reduction of androgen receptor and increased apoptosis upon treatment with piperlongumine, validating data from cell lines. We demonstrate a TSC model that authentically recapitulates the structural, cellular, and genetic characteristics of the benign and malignant human prostate, androgen-dependence of the native tissue, and cancer-specific response to a potential new therapeutic for PCa. The work described herein provides a basis for advancing the experimental utility of the TSC model. |
format | Online Article Text |
id | pubmed-3946793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-39467932014-08-01 Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate Maund, Sophia L. Nolley, Rosalie Peehl, Donna M. Lab Invest Article Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro and in vivo models. “Tissue slice cultures” (TSC) provide realistic preclinical models of diverse tissues and organs, but have not been fully developed or widely utilized for prostate studies. Problems encountered include degeneration of differentiated secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we optimized, characterized, and applied a TSC model of primary human PCa and benign prostate tissue that overcomes many deficiencies of current in vitro models. Tissue cores from fresh prostatectomy specimens were precision-cut at 300-µm and incubated in a rotary culture apparatus. The ability of varied culture conditions to faithfully maintain benign and cancer cell and tissue structure and function over time was evaluated by immunohistological and biochemical assays. After optimization of the culture system, molecular and cellular responses to androgen ablation and to piperlongumine, purported to specifically reduce androgen signaling in PCa, were investigated. Optimized culture conditions successfully maintained the structural and functional fidelity of both benign and PCa TSCs for 5 days. TSCs exhibited androgen-dependence, appropriately undergoing ductal degeneration, reduced proliferation, and decreased prostate-specific antigen expression upon androgen ablation. Furthermore, TSCs revealed cancer-specific reduction of androgen receptor and increased apoptosis upon treatment with piperlongumine, validating data from cell lines. We demonstrate a TSC model that authentically recapitulates the structural, cellular, and genetic characteristics of the benign and malignant human prostate, androgen-dependence of the native tissue, and cancer-specific response to a potential new therapeutic for PCa. The work described herein provides a basis for advancing the experimental utility of the TSC model. 2013-12-02 2014-02 /pmc/articles/PMC3946793/ /pubmed/24296879 http://dx.doi.org/10.1038/labinvest.2013.141 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Maund, Sophia L. Nolley, Rosalie Peehl, Donna M. Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title | Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title_full | Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title_fullStr | Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title_full_unstemmed | Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title_short | Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
title_sort | optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946793/ https://www.ncbi.nlm.nih.gov/pubmed/24296879 http://dx.doi.org/10.1038/labinvest.2013.141 |
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