Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis
The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of fu...
| Main Authors: | , , |
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| Format: | Journal Article |
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Hindawi Publishing Corporation
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/40859 |
| _version_ | 1848755983944253440 |
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| author | Broadhead, M. Choong, P. Dass, Crispin |
| author_facet | Broadhead, M. Choong, P. Dass, Crispin |
| author_sort | Broadhead, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent. |
| first_indexed | 2025-11-14T09:04:59Z |
| format | Journal Article |
| id | curtin-20.500.11937-40859 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:04:59Z |
| publishDate | 2012 |
| publisher | Hindawi Publishing Corporation |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-408592017-09-13T14:03:54Z Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis Broadhead, M. Choong, P. Dass, Crispin The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent. 2012 Journal Article http://hdl.handle.net/20.500.11937/40859 10.1155/2012/230298 Hindawi Publishing Corporation fulltext |
| spellingShingle | Broadhead, M. Choong, P. Dass, Crispin Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title | Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title_full | Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title_fullStr | Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title_full_unstemmed | Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title_short | Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis |
| title_sort | efficacy of continuously administered pedf-derived synthetic peptides against osteosarcoma growth and metastasis |
| url | http://hdl.handle.net/20.500.11937/40859 |