Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation
Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation
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DOI：
10.1002/cncr.21978
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发表时间：
2006-07-15
期刊：
影响因子：
6.2
通讯作者：
Rabbani, Shafaat A.
中科院分区：
文献类型：
--
作者：
Chen, Gaoping;Sircar, Kanishka;Rabbani, Shafaat A.
背景晚期前列腺癌患者对激素治疗是难治的，并且表现出发生骨转移的高倾向。在这方面，属于肿瘤坏死因子（TNF）家族的一种新型细胞因子系统的作用是潜在的兴趣，该系统对骨细胞溶解至关重要，由NF-κ B配体受体激活因子（RANKL）、其受体（RANK）和诱饵受体骨保护素（OPG）组成。逆转录聚合酶链反应（RT-PCR）和免疫组化分析用于检测RANKL、RANK和OPG在人前列腺癌细胞系和89例原发性和转移性（淋巴结、骨骼）前列腺癌患者存档样本中的表达。这些蛋白的表达与前列腺癌的临床病理参数相关。RANKL/RANK/OPG在正常前列腺癌细胞系中表达较低，而在前列腺癌细胞系中表达明显增高。手术活检标本的分析显示，RANKL（31%），RANK（38%）和OPG（19%）在原发性癌的表达。转移性前列腺癌的表达频率显著较高（RANKL [44%]、RANK [49%]和OPG [73%]）。与淋巴结转移（46%）相比，骨转移中OPG（83%）的产生更常见，而骨转移（47%）和淋巴结转移（36%）中RANKL表达的不一致性较小。RANKL/RANK/ OPG的表达与前列腺癌患者的Gleason评分、TNM分期、雄激素水平和血清前列腺特异性抗原（PSA）水平相关。RANKL/RANK/OPG的表达与更具侵袭性、晚期、转移性前列腺癌相关，提示其作为前列腺癌诊断、预后和治疗靶点的作用。
BACKGROUND. Late-stage prostate cancer patients are refractory to hormone therapy and exhibit a high propensity to develop skeletal metastasis. In this regard, the role of a novel cytokine system belonging to the tumor necrosis factor (TNF) family that is critical for osteoclastic osteolysis and that consists of receptor activator of NF-kappa B ligand (RANKL), its receptor (RANK), and decoy receptor osteoprotegerin (OPG) is of potential interest.METHODS. Reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical analysis was used to examine the expression of RANKL, RANK, and OPG in human prostate cancer cell lines and in 89 archival samples of primary and metastatic (lymph nodes, skeleton) prostate cancer patients. Expression of these proteins was correlated with clinicopathogic parameters of the prostate cancer.RESULTS. Expression of RANKL/RANK/OPG was low in normal but markedly higher in prostate cancer cell lines. Analysis of surgical biopsy specimens showed the expression of RANKL (31%), RANK (38%), and OPG (19%) in primary carcinoma. The expression frequency was significantly higher (RANKL [44%], RANK [49%], and OPG [73%]) in metastatic prostate cancer. OPG (83%) production was more common in skeletal as compared with lymph node metastases (46%), whereas the expression of RANKL expression was less discordant in bone (47%) and lymph node metastases (36%). The increased expression of RANKL/RANK/ OPG observed correlated with Gleason score, TNM stage, androgen status, and serum prostate-specific antigen (PSA) levels in the prostate cancer patients.CONCLUSIONS. Expression of RANKL/RANK/OPG correlates with more aggressive, advanced, metastatic prostate carcinoma to suggest their role as diagnostic, prognostic, and therapeutic targets for prostate cancer.