title: Characterization of neuroblastoma bone invasion/metastasis in established bone metastatic model of SY5Y and KCNR cell lines.
abstract: OBJECTIVE
  To determine the mechanism of neuroblastoma (NB) bone invasion/metastasis, it is necessary to investigate the bone invasion/metastasis-related factors in the bone invasion/metastasis process. Some evidence has suggested that various proteins were involved in bone osteolytic response. The invasion/metastasis property and gene expression of NB, however, are still unknown.
  
  
  METHODS
  Single-cell suspensions of SY5Y and KCNR cells were injected directly into the femur of nude mice. Radiological and histological analyses, immunohistochemistry analyses, and western blot assay were performed to characterize bone metastasis mechanism in these bone metastasis models.
  
  
  RESULTS
  SY5Y and KCNR NB cells result in osteolytic responses in bone metastasis model. Osteoprotegerin (OPG), receptor activator of NF-kappaB ligand (RANKL), parathyroid hormone-related peptide (PTHrP), endothelin 1 (ET-1), and CXCR4 were examined and compared among in vitro, in vivo, and normal bone, respectively. PTHrP, OPG, RANKL, and ET-1 except CXCR4 in SY5Y and KCNR NB cells xenografts were strikingly upregulated compared with normal bone and NB cells. However, significantly stronger expression of PTHrP and RANKL was presented than ET-1 and OPG; furthermore, the ratios of expression of PTHrP, RANKL to OPG, and ET-1 were also markedly increased in vivo versus in vitro.
  
  
  CONCLUSIONS
  Our study provided evidence that NB cell may enhance bone invasion through PTHrP, OPG, RANKL, and ET-1, especially PTHrP and RANKL which may display stronger effects. CXCR4 appeared not participating in bone invasion, but in tumor growth, and homing to bone. Targeting PTHrP, OPG, ET-1, and RANKL may provide a new insight and method for patient therapy by inhibiting NB bone metastasis and invasiveness.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China. zhaocmu1974@yahoo.com.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Zuke
authors.initials: Z
authors.lastname: Da
authors.affiliation: Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Hanxue
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Yaoxin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Debao
authors.initials: D
authors.lastname: Zhi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D019332:Endothelin-1 / Q000378:metabolism*; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis; D053244:Osteoprotegerin / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; D019718:Receptors, CXCR4
keywords: Bone invasion/metastasis; Invasion/metastasis-related factors; Neuroblastoma; Osteolytic response
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