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dc.contributor.authorBroadhead, M.
dc.contributor.authorDass, Crispin
dc.contributor.authorChoong, P.
dc.identifier.citationBroadhead, M. and Dass, C. and Choong, P. 2011. Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model. British Journal of Cancer. 105: pp. 1503-1511.

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.

dc.publisherNature Publishing Group
dc.titleSystemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
dc.typeJournal Article
dcterms.source.titleBritish Journal of Cancer
curtin.accessStatusOpen access via publisher

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