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Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.

Broadhead ML, Choong PF, Dass CR - J. Biomed. Biotechnol. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Department of Surgery, St. Vincent's Hospital, University of Melbourne, Fitzroy VIC 3065, Australia. matthew.broadhead@gmail.com

ABSTRACT
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.

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Systemically delivered StVOrth-3 inhibits progression of pulmonary metastatic disease. (a) Haematoxylin- and eosin-stained sections of lung tissue show micrometastases (arrows) disrupting the native alveolar architecture. Metastatic lesions were predominately subpleural and around larger airways. (b) Number of pulmonary micrometastases per lung section at 20x magnification (±SEM). (c) Cross-sectional areas of pulmonary micrometastases (±SEM). *P < 0.05, one-way ANOVA.
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fig5: Systemically delivered StVOrth-3 inhibits progression of pulmonary metastatic disease. (a) Haematoxylin- and eosin-stained sections of lung tissue show micrometastases (arrows) disrupting the native alveolar architecture. Metastatic lesions were predominately subpleural and around larger airways. (b) Number of pulmonary micrometastases per lung section at 20x magnification (±SEM). (c) Cross-sectional areas of pulmonary micrometastases (±SEM). *P < 0.05, one-way ANOVA.

Mentions: This SaOS-2 orthotopic model of osteosarcoma gives rise to spontaneous pulmonary metastases, and the burden of metastatic disease was assessed histologically post-mortem. Haematoxylin- and eosin-stained sections of lung tissue were examined under 20x objective. The numbers of micrometastases per lung section were enumerated, and treatment with StVOrth-2 or StVOrth-3, at both 50 μg/kg and 500 μg/kg doses, had no effect on the number of lesions observed (one-way ANOVA) (Figures 5(a) and 5(b)).


Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.

Broadhead ML, Choong PF, Dass CR - J. Biomed. Biotechnol. (2012)

Systemically delivered StVOrth-3 inhibits progression of pulmonary metastatic disease. (a) Haematoxylin- and eosin-stained sections of lung tissue show micrometastases (arrows) disrupting the native alveolar architecture. Metastatic lesions were predominately subpleural and around larger airways. (b) Number of pulmonary micrometastases per lung section at 20x magnification (±SEM). (c) Cross-sectional areas of pulmonary micrometastases (±SEM). *P < 0.05, one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369529&req=5

fig5: Systemically delivered StVOrth-3 inhibits progression of pulmonary metastatic disease. (a) Haematoxylin- and eosin-stained sections of lung tissue show micrometastases (arrows) disrupting the native alveolar architecture. Metastatic lesions were predominately subpleural and around larger airways. (b) Number of pulmonary micrometastases per lung section at 20x magnification (±SEM). (c) Cross-sectional areas of pulmonary micrometastases (±SEM). *P < 0.05, one-way ANOVA.
Mentions: This SaOS-2 orthotopic model of osteosarcoma gives rise to spontaneous pulmonary metastases, and the burden of metastatic disease was assessed histologically post-mortem. Haematoxylin- and eosin-stained sections of lung tissue were examined under 20x objective. The numbers of micrometastases per lung section were enumerated, and treatment with StVOrth-2 or StVOrth-3, at both 50 μg/kg and 500 μg/kg doses, had no effect on the number of lesions observed (one-way ANOVA) (Figures 5(a) and 5(b)).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics and Department of Surgery, St. Vincent's Hospital, University of Melbourne, Fitzroy VIC 3065, Australia. matthew.broadhead@gmail.com

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus