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Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia
Author(s) -
Popovics Petra,
Awadallah Wisam N.,
Kohrt Sarah E.,
Case Thomas C.,
Miller Nicole L.,
Ricke Emily A.,
Huang Wei,
RamirezSolano Marisol,
Liu Qi,
Vezina Chad M.,
Matusik Robert J.,
Ricke William A.,
Grabowska Magdalena M.
Publication year - 2020
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23986
Subject(s) - osteopontin , prostate , medicine , stromal cell , hyperplasia , lower urinary tract symptoms , prostate cancer , pathology , urology , cancer
Background Male lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells. Methods Immunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S‐BPH) or patients who underwent radical prostatectomy to remove low‐grade prostate cancer (incidental BPH, I‐BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL‐1β and TGF‐β1 was determined in stromal (BHPrS‐1) and epithelial (NHPrE‐1 and BHPrE‐1) cells by enzyme‐linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN. Results OPN immunostaining and protein levels were more abundant in S‐BPH than I‐BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF‐β1 stimulated OPN secretion by NHPrE‐1 cells and both IL‐1β and TGF‐β1 stimulated OPN secretion by BHPrS‐1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2 , and IL6 in BHPrS‐1, but not in epithelial cell lines. Conclusions OPN is more abundant in prostates of men with S‐BPH compared to men with I‐BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.