Wei Chen1, Laura E Pascal1, Ke Wang1,2, Rajiv Dhir3,4, Alexa M Sims1, Robert Campbell1, Gwenyth Gasper1, Donald B DeFranco5,6, Naoki Yoshimura1,5, Zhou Wang1,5,6. 1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 2. Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shangxi, China. 3. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 4. UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 5. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 6. Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease characterized by nonmalignant abnormal growth of the prostate, which is also frequently associated with lower urinary tract symptoms. The prostate with BPH exhibits enhanced growth not only in the epithelium but also in the stroma, and stromal-epithelial interactions are thought to play an important role in BPH pathogenesis. However, our understanding of the mechanisms of stromal-epithelial interactions in the development and progression of BPH is very limited. METHODS: Matched pairs of glandular BPH and normal adjacent prostate specimens were obtained from BPH patients undergoing simple prostatectomy for symptomatic BPH. Tissues were divided further into fresh specimens for culture of primary prostatic stromal cells, and specimens were embedded in paraffin for immunohistochemical analyses. Proliferation assays, immunohistochemistry, and immunoblotting were used to characterize the primary prostate stromal cells and tissue sections. Coculture of the primary stromal cells with benign human prostate epithelial cell lines BHPrE1 or BPH-1 was performed in three-dimensional (3D) Matrigel to determine the impact of primary stromal cells derived from BPH on epithelial proliferation. The effect of stromal-conditioned medium (CM) on BHPrE1 and BPH-1 cell growth was tested in 3D Matrigel as well. RESULTS: BPH stromal cells expressed less smooth muscle actin and calponin and increased vimentin, exhibiting a more fibroblast and myofibroblast phenotype compared with normal adjacent stromal cells both in culture and in corresponding paraffin sections. Epithelial spheroids formed in 3D cocultures with primary BPH stromal cells were larger than those formed in coculture with primary normal stromal cells. Furthermore, CM from BPH stromal cells stimulated epithelial cell growth while CM from normal primary stromal cells did not in 3D culture. CONCLUSIONS: These findings suggest that the stromal cells in BPH tissues are different from normal adjacent stromal cells and could promote epithelial cell proliferation, potentially contributing to the development and progression of BPH.
BACKGROUND:Benign prostatic hyperplasia (BPH) is an age-related disease characterized by nonmalignant abnormal growth of the prostate, which is also frequently associated with lower urinary tract symptoms. The prostate with BPH exhibits enhanced growth not only in the epithelium but also in the stroma, and stromal-epithelial interactions are thought to play an important role in BPH pathogenesis. However, our understanding of the mechanisms of stromal-epithelial interactions in the development and progression of BPH is very limited. METHODS: Matched pairs of glandular BPH and normal adjacent prostate specimens were obtained from BPH patients undergoing simple prostatectomy for symptomatic BPH. Tissues were divided further into fresh specimens for culture of primary prostatic stromal cells, and specimens were embedded in paraffin for immunohistochemical analyses. Proliferation assays, immunohistochemistry, and immunoblotting were used to characterize the primary prostate stromal cells and tissue sections. Coculture of the primary stromal cells with benign human prostate epithelial cell lines BHPrE1 or BPH-1 was performed in three-dimensional (3D) Matrigel to determine the impact of primary stromal cells derived from BPH on epithelial proliferation. The effect of stromal-conditioned medium (CM) on BHPrE1 and BPH-1 cell growth was tested in 3D Matrigel as well. RESULTS: BPH stromal cells expressed less smooth muscle actin and calponin and increased vimentin, exhibiting a more fibroblast and myofibroblast phenotype compared with normal adjacent stromal cells both in culture and in corresponding paraffin sections. Epithelial spheroids formed in 3D cocultures with primary BPH stromal cells were larger than those formed in coculture with primary normal stromal cells. Furthermore, CM from BPH stromal cells stimulated epithelial cell growth while CM from normal primary stromal cells did not in 3D culture. CONCLUSIONS: These findings suggest that the stromal cells in BPH tissues are different from normal adjacent stromal cells and could promote epithelial cell proliferation, potentially contributing to the development and progression of BPH.
Authors: Antonio Palumbo; Luciana Bueno Ferreira; Pedro A V Reis de Souza; Felipe Leite de Oliveira; Bruno Pontes; Nathan B Viana; Daniel Escorsim Machado; Celia Yelimar Palmero; Leandro M Alves; Etel R P Gimba; Luiz E Nasciutti Journal: Cancer Lett Date: 2012-02-28 Impact factor: 8.679
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Authors: Chandler N Hudson; Kai He; Laura E Pascal; Teresa Liu; Livianna K Myklebust; Rajiv Dhir; Pooja Srivastava; Naoki Yoshimura; Zhou Wang; William A Ricke; Donald B DeFranco Journal: Am J Clin Exp Urol Date: 2022-08-15