Research Repository

PEDF-Derived Synthetic Peptides Exhibit Antitumor Activity in an Orthotopic Model of Human Osteosarcoma

Ek, Eugene T. H and Dass, Crispin R and Contreras, Karla G and Choong, Peter F. M (2007) PEDF-Derived Synthetic Peptides Exhibit Antitumor Activity in an Orthotopic Model of Human Osteosarcoma. Journal of Orthopaedic Research, 25 (12). pp. 1671-1680. ISSN 0736-0266

Full text for this resource is not available from the Research Repository.

Abstract

Pigment epithelium-derived factor (PEDF) is one of the most potent inhibitors of angiogenesis, and has recently been demonstrated to have an important multifunctional role in tumor growth, invasion, and metastasis. However, relatively little is known of mechanisms through which PEDF exerts its antitumor activity. Therefore, with the aim of identifying potential functional epitopes specifically against osteosarcoma, we evaluated the bioactivity of four 25-mer synthetic PEDF-derived peptides (termed StVOrth-1, -2 -3, and -4) against a human osteosarcoma cell line, SaOS-2. We found that StVOrth-2 (residues 78-102) predominantly inhibited tumor cell proliferation, while StVOrth-3 (residues 90-114) markedly increased cellular adhesion to collagen type-1, with StVOrth-4 (residues 387-411) demonstrating most significant inhibition of Matrigel invasion. Furthermore, we show that StVOrth-1 (residues 40-64), -2 and -3 induce osteoblastic differentiation, evidenced by increased mineralized nodule formation. Interestingly, although no peptide inhibited angiogenesis in the tube formation assay, StVOrth-3 and -4 markedly suppressed VEGF expression. We further tested the activity of StVOrth-2 and StVOrth-3 in vivo, in an orthotopic model of osteosarcoma and found that both peptides significantly inhibited primary tumor growth and the development of pulmonary metastases. Together these results provide greater insight into the potential mechanisms through which PEDF exerts its antitumor function. Furthermore, this raises the possibility of developing short PEDF fragments as lead compounds for the treatment of osteosarcoma.

Item Type: Article
Uncontrolled Keywords: ResPubID18881, Pigment epithelium-derived factor (PEDF), inhibitors of angiogenesis, tumor growth, tumor invasion, metastasis, osteosarcoma
Subjects: FOR Classification > 1112 Oncology and Carcinogenesis
Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Related URLs:
Depositing User: VUIR
Date Deposited: 04 May 2012 04:44
Last Modified: 04 May 2012 04:44
URI: http://vuir.vu.edu.au/id/eprint/3266
DOI: 10.1002/jor.20434
ePrint Statistics: View download statistics for this item
Citations in Scopus: 39 - View on Scopus

Repository staff only

View Item View Item

Search Google Scholar