Osteoprotegerin and rank ligand expression in prostate cancer

Osteoprotegerin and rank ligand expression in prostate cancer
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DOI:
10.1016/s0090-4295(00)01122-5
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发表时间:
2001-04-01
期刊:
影响因子:
2.1
通讯作者:
Vessella, RL
Vessella, RL
中科院分区:
医学4区
文献类型:
--
作者:
Brown, JM;Corey, E;Vessella, RL

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目标.目的探讨骨保护素(OPG)和RANK配体(RANKL)在人前列腺组织中的表达。调节与前列腺癌(CaP)骨转移相关的转换增加的因素尚不清楚。OPC和RANKL是最近确定的骨吸收和骨重建的调节剂。采用逆转录-聚合酶链反应(RT-PCR)和免疫组化方法检测28例CaP患者和4例正常器官供体组织中OPC和RANKL的表达。OPG和RANKL信息在正常和癌性前列腺样品中均被检测到。在正常前列腺中,在管腔上皮细胞和基质细胞中检测到OPG蛋白(分别为5%至65%和15%至70%),在基底上皮细胞、管腔上皮细胞和基质细胞中分别观察到15%至50%、40%至90%和70%至100%的RANKL免疫反应性。在10份原发性CaP标本中有8份未检测到OPG;在11份CaP标本中有10份RANKL呈异质性表达。与非骨转移瘤或原发性CaP相比,所有CaP骨转移瘤中表达OPG和RANKL的肿瘤细胞百分比均显著增加。与非骨转移瘤或原发性CaP相比,CaP骨转移瘤对OPG和RANKL的免疫反应一致。这些关键的骨吸收调节剂在CaP骨转移中的存在表明了CaP细胞可以调节骨转换的机制,并且对晚期疾病中CaP骨转移的建立和发展具有深远的意义。泌尿学57:611-616,2001年。(C)2001年,Elsevier Science Inc.
Objectives. To investigate the expression of osteoprotegerin (OPG) and RANK ligand (RANKL) in human prostatic tissues. The factors regulating the increased turnover associated with prostate cancer (CaP) bone metastasis are unknown. OPC and RANKL are recently identified regulators of bone resorption and bone remodeling.Methods. Tissues from 28 patients with CaP and from 4 normal organ donors were analyzed by reverse transcriptase-polymerase chain reaction and immunohistochemistry for the expression of OPC and RANKL.Results. OPG and RANKL messages were detected in both normal and cancerous prostate samples. In the normal prostate, OPG protein was detected in luminal epithelial and stromal cells (5% to 65% and 15% to 70%, respectively) and RANKL immunoreactivity was observed in 15% to 50% of basal epithelial cells, 40% to 90% of luminal epithelial cells, and 70% to 100% of stromal cells. OPG was not detected in 8 of 10 primary CaP specimens; RANKL was heterogeneously expressed in 10 of 11 CaP specimens. The percentage of tumor cells expressing OPG and RANKL was significantly increased in all CaP bone metastases compared with nonosseous metastases or primary CaP.Conclusions. CaP bone metastases were consistently immunoreactive for both OPG and RANKL compared with nonosseous metastases or primary CaP. The presence of these crucial bone resorption regulators in CaP bone metastases suggests a mechanism whereby CaP cells may modulate bone turnover and has profound implications for the establishment and development of CaP bone metastases in advanced disease. UROLOGY 57: 611-616, 2001. (C) 2001, Elsevier Science Inc.