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Updated: May 28, 2026
Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues
Published on: March 22, 2024
Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
M L Broadhead1, C R Dass, P F M Choong
1Department of Orthopaedics, St Vincent's Hospital Melbourne, Level 3, Daly Wing, 35 Victoria Pde, Fitzroy, VIC 3065, Australia.
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.
Conclusion:
Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma.
