title: Animal and cellular models of hepatocellular carcinoma bone metastasis: establishment and characterisation.
abstract: BACKGROUND
  An increasingly high occurrence of bone metastases in hepatocellular carcinoma (HCC) patients highlights the importance of fundamental research on HCC bone metastasis, which has been limited in its success due to the lack of a model system.
  
  
  OBJECTIVE
  Establishment of animal and cellular models of HCC bone metastasis and discovery of HCC bone metastasis-related genes.
  
  
  METHODS
  Luciferase-transfected HCC cell lines HCCLM3, MHCC97H, and SMMC-7721 were used to inoculate nude mice intracardially. Formation of bone metastases was examined by bioluminescence imaging, SPECT, and pathology study. Metastatic cells in bone were isolated and subcultured. Differences between bone metastatic cells and their parental cells were studied by in vitro/in vivo assays.
  
  
  RESULTS
  Mouse model of HCC bone metastasis was successfully established. Injected tumour cells formed metastases in the skull, the spine, the hind limbs, and the sternum, causing osteolytic lesions via act of MMP-1 and recruitment of osteoclasts. Four bone metastatic cell lines were extracted from HCCLM3-inoculated mice and were demonstrated to exhibit a much stronger ability to form bone metastases as well as other phenotypes, including enhanced in vitro migration/invasion and colony formation. Moreover, the expression of PTHrP, MMP-1, and CTGF was significantly elevated in bone metastatic cells compared to parental HCC cells.
  
  
  CONCLUSIONS
  The nude mouse model and bone metastatic cell lines together provide an effective simulation of HCC bone metastasis. This model system will become powerful tool with which to explore the mechanisms and therapies of HCC bone metastasis. Additionally, PTHrP, MMP-1, and CTGF are candidate genes related to HCC bone metastasis.
authors.affiliation: Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Liang
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Sixth Subsidiary Sun Yat-sen University Hospital, Guangzhou, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Bin-Hao
authors.initials: BH
authors.lastname: Zhang
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. bixiangzhang@yahoo.com.cn.
authors.forename: Bi-Xiang
authors.initials: BX
authors.lastname: Zhang
authors.affiliation: Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. chen_xiaoping52@163.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008156:Luciferases; D049408:Luminescent Agents; D008163:Luminescent Measurements; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C526318:CCN2 protein, mouse; D049408:Luminescent Agents; D044162:Parathyroid Hormone-Related Protein; D055513:Connective Tissue Growth Factor; D008156:Luciferases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
keywords: Animal model; Bone metastasis; CTGF; Cell line; Hepatocellular carcinoma; MMP-1; Osteoclasts; PTHrP
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