Department of Pathology, Oulu University Hospital, Oulu, Finland.
Prostate. 2010 Jun 1;70(8):817-24. doi: 10.1002/pros.21115.
Toll-like receptor-9 (TLR9) is a cellular receptor for bacterial and vertebrate DNA. In addition to cells of the immune system, it is also expressed in various human cancer cell lines, including prostate cancer. We demonstrated previously that synthetic TLR9 ligands induce matrix metalloproteinase-13-mediated invasion in TLR9-expressing prostate cancer cells in vitro. Other studies have suggested possible sex steroid regulation of the function of the various TLRs. The role of TLR9 in the pathophysiology of prostate or any cancer is, however, unknown.
Expression of TLR9, androgen receptor (AR), or the estrogen receptors alpha (ERalpha) and beta (ERbeta) were studied with immunohistochemistry in prostate cancer (n = 62) and benign prostatic hyperplasia (n = 45) specimens. TLR9 staining scores were compared with tumor stage, Gleason score, prostate-specific antigen (PSA) concentrations before tissue sampling and with the staining scores of AR, ERalpha, and ERbeta.
TLR9 expression was statistically significantly increased in prostate cancer epithelium and stroma, as compared with the same cellular compartments in benign hyperplasia. Significantly increased (P = 0.04) TLR9 expression was detected in cancers with high Gleason score (>7, n = 23), as compared with lower Gleason scores (< or =7, n = 39). No statistically significant associations were detected between TLR9 expression scores and PSA concentrations or tumor staging. Prostate adenocarcinoma cells were all positive for TLR9, AR, and ERbeta but negative for ERalpha expression. In cancer stroma cells, increased TLR9 expression was associated with increased ERalpha expression.
Expression of TLR9 is increased in prostate cancer specimens, especially in the most poorly differentiated forms.
Toll 样受体-9（TLR9）是细菌和脊椎动物 DNA 的细胞受体。除了免疫系统的细胞外，它还在各种人类癌细胞系中表达，包括前列腺癌。我们之前证明，合成 TLR9 配体在体外诱导 TLR9 表达的前列腺癌细胞中基质金属蛋白酶-13 介导的侵袭。其他研究表明，各种 TLR 的功能可能受到性激素的调节。然而，TLR9 在前列腺或任何癌症的病理生理学中的作用尚不清楚。
用免疫组织化学法检测前列腺癌（n = 62）和良性前列腺增生（n = 45）标本中 TLR9、雄激素受体（AR）以及雌激素受体α（ERα）和β（ERβ）的表达。将 TLR9 染色评分与肿瘤分期、Gleason 评分、组织取样前前列腺特异性抗原（PSA）浓度以及 AR、ERα 和 ERβ 的染色评分进行比较。
与良性增生的相同细胞区室相比，TLR9 在前列腺癌上皮和基质中的表达统计学上显著增加。与 Gleason 评分较低（<或=7，n = 39）相比，Gleason 评分较高（>7，n = 23）的癌症中检测到 TLR9 表达显著增加（P = 0.04）。TLR9 表达评分与 PSA 浓度或肿瘤分期之间未检测到统计学显著相关性。前列腺腺癌细胞均对 TLR9、AR 和 ERβ 呈阳性，但对 ERα 表达呈阴性。在癌症基质细胞中，TLR9 表达的增加与 ERα 表达的增加相关。
TLR9 在前列腺癌标本中的表达增加，特别是在分化最差的形式中。
