Limits...
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.

Show MeSH

Related in: MedlinePlus

Tumour invasion. Plain radiographs (left) of tumour-bearing limbs show extensive osteolysis of proximal tibiae and soft tissue extension for all treatment groups. Haematoxylin and eosin-stained sections of orthotopic tumour (right) show tumour cells (T) invading bone (B) and skeletal muscle (M).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3369529&req=5

fig4: Tumour invasion. Plain radiographs (left) of tumour-bearing limbs show extensive osteolysis of proximal tibiae and soft tissue extension for all treatment groups. Haematoxylin and eosin-stained sections of orthotopic tumour (right) show tumour cells (T) invading bone (B) and skeletal muscle (M).

Mentions: Plain radiographs obtained after disarticulation of tumour-bearing limbs showed extensive soft tissue invasion and osteolysis for all animals (Figure 4). Invasion of surrounding structures, tumour necrosis, and apoptosis were assessed histologically. Treatment with either StVOrth-2 or StVOrth-3, at both 50 μg/kg and 500 μg/kg doses, did not affect orthotopic tumour invasion of the surrounding structures. All tumour-bearing animals showed invasion of skeletal muscles and osteolysis on both sides of the adjacent joint. Tumour cells were clearly seen breaching the epiphyseal cartilage (Figure 4).


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

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

Tumour invasion. Plain radiographs (left) of tumour-bearing limbs show extensive osteolysis of proximal tibiae and soft tissue extension for all treatment groups. Haematoxylin and eosin-stained sections of orthotopic tumour (right) show tumour cells (T) invading bone (B) and skeletal muscle (M).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Tumour invasion. Plain radiographs (left) of tumour-bearing limbs show extensive osteolysis of proximal tibiae and soft tissue extension for all treatment groups. Haematoxylin and eosin-stained sections of orthotopic tumour (right) show tumour cells (T) invading bone (B) and skeletal muscle (M).
Mentions: Plain radiographs obtained after disarticulation of tumour-bearing limbs showed extensive soft tissue invasion and osteolysis for all animals (Figure 4). Invasion of surrounding structures, tumour necrosis, and apoptosis were assessed histologically. Treatment with either StVOrth-2 or StVOrth-3, at both 50 μg/kg and 500 μg/kg doses, did not affect orthotopic tumour invasion of the surrounding structures. All tumour-bearing animals showed invasion of skeletal muscles and osteolysis on both sides of the adjacent joint. Tumour cells were clearly seen breaching the epiphyseal cartilage (Figure 4).

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