Co‐expression of TLR‐9 and MMP‐13 is associated with the degree of tumour differentiation in prostate cancer

• Published in: International journal of experimental pathology Vol. 100; no. 2; pp. 123 - 132
• Main Authors: Kalantari, Elham, Abolhasani, Maryam, Roudi, Raheleh, Farajollahi, Mohammad M., Farhad, Seif, Madjd, Zahra, Askarian‐Amiri, Shaghayegh, Mohsenzadegan, Monireh
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2019; John Wiley and Sons Inc
• Subjects: Adult; Aged; Aged, 80 and over; Benign; benign prostatic hyperplasia; Biomarkers, Tumor - metabolism; Biopsy; Cell Differentiation; Collagenase 3; high‐grade prostatic intraepithelial neoplasia; Humans; Hyperplasia; Lymph nodes; Lymphatic Metastasis; Male; Markers; Matrix metalloproteinase; Matrix Metalloproteinase 13 - metabolism; Matrix metalloproteinases; Metalloproteinase; Middle Aged; MMP‐13; Neoplasm Grading; Neoplasm Proteins - metabolism; Original; Phenotypes; Prostate cancer; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Prostatic intraepithelial neoplasia; Prostatic Intraepithelial Neoplasia - metabolism; Prostatic Intraepithelial Neoplasia - pathology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tissues; TLR‐9; Toll-Like Receptor 9 - metabolism; Toll-like receptors; Tumors; MMP-13; high-grade prostatic intraepithelial neoplasia; prostate cancer; TLR-9; benign prostatic hyperplasia
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/iep.12314

Summary In vitro experiments demonstrated that stimulation of Toll‐like receptor 9 (TLR‐9) by synthetic TLR‐9 ligands induces the invasion of TLR‐9‐expressing prostate cancer cells through matrix metalloproteinase 13 (MMP‐13). However, the clinical value of TLR‐9 and MMP‐13 co‐expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR‐9 and MMP‐13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high‐grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR‐9 and MMP‐13 markers. Subsequently, the correlation between the TLR‐9 and MMP‐13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR‐9 and MMP‐13 were found in PCa and high‐grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP‐13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR‐9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR‐9 and MMP‐13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR‐9high/MMP‐13high and TLR‐9low/MMP‐13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR‐9 and MMP‐13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.