title: Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model.
abstract: BACKGROUND
  Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods.
  
  
  METHODS
  In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump.
  
  
  RESULTS
  In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues.
  
  
  CONCLUSIONS
  Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma.
authors: Department of Orthopaedics, St Vincent's Hospital Melbourne, Level 3, Daly Wing, 35 Victoria Pde, Fitzroy, VIC 3065, Australia.
authors: M L
authors: ML
authors: Broadhead
authors: C R
authors: CR
authors: Dass
authors: P F M
authors: PF
authors: Choong
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy*; D015843:Serpins / Q000008:administration & dosage / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor