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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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Related in: MedlinePlus

StVOrth-2 and StVOrth-3 peptides. StVOrth-2 (highlighted in blue) consists of residues 78–102 of the parent PEDF sequence. StVOrth-3 (highlighted in red) consists of residues 90–114. StVOrth-2 and StVOrth-3 have previously been shown to inhibit osteosarcoma cell proliferation and promote osteosarcoma cell adhesion to collagen I in vitro, respectively [7]. *ERT and 44-mer peptide sequences, as described by Filleur et al. [6], overlap with the StVOrth-2 and StVOrth-3 sequences.
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fig1: StVOrth-2 and StVOrth-3 peptides. StVOrth-2 (highlighted in blue) consists of residues 78–102 of the parent PEDF sequence. StVOrth-3 (highlighted in red) consists of residues 90–114. StVOrth-2 and StVOrth-3 have previously been shown to inhibit osteosarcoma cell proliferation and promote osteosarcoma cell adhesion to collagen I in vitro, respectively [7]. *ERT and 44-mer peptide sequences, as described by Filleur et al. [6], overlap with the StVOrth-2 and StVOrth-3 sequences.

Mentions: In another study, four different PEDF-derived peptides, termed StVOrth-1, StVOrth-2, StVOrth-3, and StVOrth-4, consisting of PEDF residues 40–64, 78–102, 90–114, and 387–411, respectively, were tested in vitro and in vivo [7]. In vitro, StVOrth-2 was the most potent inhibitor of SaOS-2 osteosarcoma cell proliferation, while StVOrth-3 dramatically promoted SaOS-2 adhesion to collagen I. StVOrth-4 inhibited SaOS-2 cell invasion through Matrigel. StVOrth-1, -2, and -3 all induced osteoblastic differentiation. StVOrth-3 and StVOrth-4 reduced VEGF expression in SaOS-2 osteosarcoma cells. StVOrth-2 and StVOrth-3 were then evaluated in vivo using an orthotopic murine model of osteosarcoma. Notably, StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) possessed sequences that overlapped with the 44-mer (residues 58–101) and ERT (residues 79–94) sequences described by Filleur et al. [6] (Figure 1). Both StVOrth-2 and StVOrth-3 restricted osteosarcoma tumour growth and inhibited the development of pulmonary metastases when SaOS-2 cells were treated prior to intratibial injection.


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

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

StVOrth-2 and StVOrth-3 peptides. StVOrth-2 (highlighted in blue) consists of residues 78–102 of the parent PEDF sequence. StVOrth-3 (highlighted in red) consists of residues 90–114. StVOrth-2 and StVOrth-3 have previously been shown to inhibit osteosarcoma cell proliferation and promote osteosarcoma cell adhesion to collagen I in vitro, respectively [7]. *ERT and 44-mer peptide sequences, as described by Filleur et al. [6], overlap with the StVOrth-2 and StVOrth-3 sequences.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: StVOrth-2 and StVOrth-3 peptides. StVOrth-2 (highlighted in blue) consists of residues 78–102 of the parent PEDF sequence. StVOrth-3 (highlighted in red) consists of residues 90–114. StVOrth-2 and StVOrth-3 have previously been shown to inhibit osteosarcoma cell proliferation and promote osteosarcoma cell adhesion to collagen I in vitro, respectively [7]. *ERT and 44-mer peptide sequences, as described by Filleur et al. [6], overlap with the StVOrth-2 and StVOrth-3 sequences.
Mentions: In another study, four different PEDF-derived peptides, termed StVOrth-1, StVOrth-2, StVOrth-3, and StVOrth-4, consisting of PEDF residues 40–64, 78–102, 90–114, and 387–411, respectively, were tested in vitro and in vivo [7]. In vitro, StVOrth-2 was the most potent inhibitor of SaOS-2 osteosarcoma cell proliferation, while StVOrth-3 dramatically promoted SaOS-2 adhesion to collagen I. StVOrth-4 inhibited SaOS-2 cell invasion through Matrigel. StVOrth-1, -2, and -3 all induced osteoblastic differentiation. StVOrth-3 and StVOrth-4 reduced VEGF expression in SaOS-2 osteosarcoma cells. StVOrth-2 and StVOrth-3 were then evaluated in vivo using an orthotopic murine model of osteosarcoma. Notably, StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) possessed sequences that overlapped with the 44-mer (residues 58–101) and ERT (residues 79–94) sequences described by Filleur et al. [6] (Figure 1). Both StVOrth-2 and StVOrth-3 restricted osteosarcoma tumour growth and inhibited the development of pulmonary metastases when SaOS-2 cells were treated prior to intratibial injection.

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