title: Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Tingting
authors.initials: T
authors.lastname: Ren
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lou
authors.forename: Xinchang
authors.initials: X
authors.lastname: Lu
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Qunshan
authors.initials: Q
authors.lastname: Lu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000175:diagnosis / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D064847:Multimodal Imaging; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D049268:Positron-Emission Tomography; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B