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

Abstract

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.

The prognostic value and potential mechanism of Matrix Metalloproteinases among Prostate Cancer

“…Kalantari et al . 34 revealed the bipartite function of MMP13 and TLR-9, patients with the high expression of MMP13 and TLR-9 showed an advanced stage of PCa. The status of CRPC and medicine resistance are the hot potatoes for the clinical treatment of PCa patients.…”

“…Ganguly et al [33] found that Notch3 could promote the bone metastasis of PCa patients throng MMP3 mediated osteoblastic lesion formation. Kalantari et al [34] revealed the bipartite function of MMP13 and TLR-9, patients with the high expression of MMP13 and TLR-9 showed an advanced stage of PCa. The status of CRPC and medicine resistance are the hot potatoes for the clinical treatment of PCa patients.…”

The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review

“…However, other studies have reported associations between expression and PrCa [ 46 ], including grade/stage [ 105 , 139 ] and metastatic properties, with MMP-1 ablation shown to reduce invasion [ 154 ]. Similarly, MMP-13 expression has typically not been associated with PrCa [ 31 , 48 , 84 , 91 , 95 ], but some studies do provide evidence of this [ 50 , 52 , 70 ]. Publications investigating MMP-11 also range from identifying no correlation [ 91 ] to a negative correlation [ 83 ] to a positive correlation [ 45 , 48 ], while the only study on MMP-23 points toward a negative correlation [ 115 ].…”

Nuclear overexpression levels of MAGE‐A3 predict poor prognosis in patients with prostate cancer

“…The overall median age of these three groups was 66 years, which is the range from 48 to 90 years. Serum PSA levels in PCa patients (before surgery and receiving systemic treatment) were divided into three groups: less than 4 ng / ml, between 4 and 10 ng / ml, and more than 10 ng / ml (range 6-352, median :9 ng/mL) (20). Of the 90 PCa patients whose PSA level information was available, 6 cases (6.7%) had a PSA of < 4 ng / ml, 46 cases (51.1%) 4 to 10 ng / ml and 38 cases (42.2%) > 10 ng / ml.…”