Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer.
Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0058361
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Peng X;Guo W;Ren T;Lou Z;Lu X;Zhang S;Lu Q;Sun Y
人非小细胞肺癌（NSCLC）患者表现出发生骨转移的高倾向，导致过度的溶骨活性。RANKL/RANK/OPG系统通过调节破骨细胞的形成和活性在骨重建中起关键作用，在这方面具有潜在的意义。采用逆转录聚合酶链反应、免疫印迹和免疫组织化学方法检测RANKL、RANK和OPG在不同转移潜能的人NSCLC细胞系中的表达，以及在52例原发性NSCLC和75例NSCLC骨转移标本中的表达。在原发性NSCLC患者中，这些蛋白的表达与临床病理参数相关。将重组人RANKL和转染的RANKL cDNA加入PAa细胞系中，以评价RANKL在体外和体内转移过程中的启动子作用。在NSCLC细胞系和骨转移肿瘤组织中检测到RANKL、RANK和OPG表达上调以及RANKL：OPG比值升高，并与较高的转移潜能相关。重组人RANKL和转染RANKL cDNA均能显著增强NSCLC的体内外转移能力，包括迁移和侵袭能力，而加入OPG后，这种转移能力被削弱。RANKL和OPG的表达与肿瘤分期、淋巴结转移和远处转移有关。RANKL、RANK和OPG的差异表达与人NSCLC向骨骼的转移潜力相关，这增加了RANKL/RANK/OPG系统可能成为治疗转移性NSCLC患者的治疗靶点的可能性。
Human non-small cell lung cancer (NSCLC) patients exhibit a high propensity to develop skeletal metastasis, resulting in excessive osteolytic activity. The RANKL/RANK/OPG system, which plays a pivotal role in bone remodeling by regulating osteoclast formation and activity, is of potential interest in this context. Reverse transcriptase polymerase chain reaction, western blotting, and immunohistochemical analysis were used to examine the expression of RANKL, RANK, and OPG in human NSCLC cell lines with different metastatic potentials, as well as in 52 primary NSCLC samples and 75 NSCLC bone metastasis samples. In primary NSCLC patients, the expression of these proteins was correlated with clinicopathological parameters. Recombinant human RANKL and transfected RANKL cDNA were added to the PAa cell line to evaluate the promoter action of RANKL during the process of metastasis in vitro and in vivo. Up-regulated RANKL, RANK, and OPG expression and increased RANKL:OPG ratio were detected in NSCLC cell lines and in tumor tissues with bone metastasis, and were correlated with higher metastatic potential. The metastatic potential of NSCLC in vitro and in vivo, including migration and invasion ability, was significantly enhanced by recombinant human RANKL and the transfection of RANKL cDNA, and was impaired after OPG was added. The increased expression of RANKL and OPG correlated with tumor stage, lymph node metastasis, and distant metastasis. Differential expression of RANKL, RANK, and OPG is associated with the metastatic potential of human NSCLC to skeleton, raising the possibility that the RANKL/RANK/OPG system could be a therapeutic target for the treatment of metastatic NSCLC patients.
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DOI：
10.1097/01.blo.0000092979.12414.54
发表时间：
2003-10-01
影响因子：
4.2
作者：
Demers, LM;Costa, L;Lipton, A
通讯作者：
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影响因子：
3.4
作者：
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影响因子：
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作者：
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通讯作者：
Rabbani, Shafaat A.
DOI：
10.1006/bbrc.1998.9788
发表时间：
1998-12-18
影响因子：
3.1
作者：
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通讯作者：
Higashio, K
影响因子：
3.8
作者：
Holen, I;Cross, SS;Eaton, CL
通讯作者：
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