title: [Retros Flt-1 decelerates the growth of a murine experimental osteosarcoma].
abstract: OBJECTIVE
  To examine the influence of vascular endothelial growth factors (VEGF) in controlling the growth of an experimental osteosarcoma in mice by performing retrovirus-mediated sFlt-1 gene modification.
  
  
  METHODS
  From March to October 2010 human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses.
  
  
  RESULTS
  Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue.
  
  
  CONCLUSIONS
  Retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.
authors.affiliation: Department of Orthopaedic Surgery, Weihai Municipal Hospital, Weihai, China.
authors.forename: Xiao-tang
authors.initials: XT
authors.lastname: Xin
authors.forename: De-zhen
authors.initials: DZ
authors.lastname: Yin
authors.forename: Hai
authors.initials: H
authors.lastname: Lan
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Shang-you
authors.initials: SY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007763:Lac Operon; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012190:Retroviridae / Q000235:genetics*; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1