Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model

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 ch...

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Main Authors: Broadhead, M., Dass, Crispin, Choong, P.
Format: Journal Article
Published: Nature Publishing Group 2011
Online Access:http://hdl.handle.net/20.500.11937/19073
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author Broadhead, M.
Dass, Crispin
Choong, P.
author_facet Broadhead, M.
Dass, Crispin
Choong, P.
author_sort Broadhead, M.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-190732017-09-13T13:46:48Z Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model Broadhead, M. Dass, Crispin Choong, P. 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. 2011 Journal Article http://hdl.handle.net/20.500.11937/19073 10.1038/bjc.2011.410 Nature Publishing Group unknown
spellingShingle Broadhead, M.
Dass, Crispin
Choong, P.
Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title_full Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title_fullStr Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title_full_unstemmed Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title_short Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model
title_sort systemically administered pedf against primary and secondary tumours in a clinically relevant osteosarcoma model
url http://hdl.handle.net/20.500.11937/19073