title: Basigin-2 upregulated by receptor activator of NF-κB ligand enhances lung cancer-induced osteolytic lesions.
abstract: BACKGROUND
  Lung cancer bone metastasis causes poor prognosis. Basigin-2, a novel cancer-associated biomarker, is upregulated in lung cancer and has been linked with tumor progression. But little is known about the role of basigin-2 in lung cancer bone metastasis and osteolytic lesion.
  
  
  METHODS
  Basigin-2 expression was evaluated in biopsy tissue specimens of 20 lung cancer patients with bone metastases via immunohistochemistry. Invasion assay and MTT proliferation assay were performed to test the invasion and proliferation of lung cancer cell after modulated basigin-2 expression. The osteoclastic activity of basigin-2 was detected in tibia cancer model by injected of lung cancer cells. The regulation role of receptor activator of NF-κB ligand (RANKL) on basigin-2 and its downstream molecules were measured by real-time quantitative RT-PCR, gelatin zymography and western blot analysis.
  
  
  RESULTS
  We found that basigin-2 was highly expressed in lung cancer bone metastases. Then, we demonstrated that basigin-2 could promote lung cancer cells invasion, metastasis and proliferation through upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression. The lung cancer cells overexpressing basigin-2 strongly induced the osteolytic lesions in immunodeficient mice, which were reduced by treatment with basigin-2 blocking antibody. Furthermore, we explored the enhanced basigin-2 molecular mechanism in lung cancer bone metastasis. Our results indicated the RANKL, pivotal for the control of bone resorption, could increase basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro.
  
  
  CONCLUSIONS
  Basigin-2 upregulated by RANKL induces MMPs and VEGF, which may increase lung cancer cell metastasis ability and support osteoclastic activity. Thus, our data suggest important roles for basigin-2 in lung cancer-induced osteolytic lesion and implicate this protein potential application as a target for lung cancer bone metastasis therapy.
authors.affiliation: Department of Oncology, Tangdu Hospital, Cancer Institute, Fourth Military Medical University, Xi'an, 710038 People's Republic of China.|Department of Oncology, Urumqi General Hospital of Lanzhou Military Command of PLA, Urumqi, 830000 People's Republic of China.
authors.forename: Cheng-Gong
authors.initials: CG
authors.lastname: Liao
authors.affiliation: Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038 People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Oncology, Urumqi General Hospital of Lanzhou Military Command of PLA, Urumqi, 830000 People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Oncology, Tangdu Hospital, Cancer Institute, Fourth Military Medical University, Xi'an, 710038 People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cadet Brigade, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
authors.forename: Sheng-Da
authors.initials: SD
authors.lastname: Wu
authors.affiliation: Department of Oncology, Urumqi General Hospital of Lanzhou Military Command of PLA, Urumqi, 830000 People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Oncology, Urumqi General Hospital of Lanzhou Military Command of PLA, Urumqi, 830000 People's Republic of China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Huang
authors.affiliation: Cell Engineering Research Center and Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
authors.forename: Ling-Min
authors.initials: LM
authors.lastname: Kong
authors.affiliation: Department of Oncology, Tangdu Hospital, Cancer Institute, Fourth Military Medical University, Xi'an, 710038 People's Republic of China.
authors.forename: He-Long
authors.initials: HL
authors.lastname: Zhang
keywords: Basigin-2; Bone metastasis; Lung cancer; Osteolytic lesion; RANKL