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.