PEDF as an Emerging Therapeutic Candidate for Osteosarcoma

Crispin   R.   Dass; Eugene   T.H.   Ek; Peter   F.M.   Choong

Abstract

Osteosarcoma (OS) is a disease that afflicts teenagers and adolescents in the prime of their lives. In spite of surgery and therapies currently used, there is a 1/3 chance of relapse. As for other cancers, current research is largely devoted to elucidating the molecular basis of the disease, with the anticipation that such research will lead to discovery and development of biological therapies. The major advantage of utilising such therapy is the relative lack of toxicity to normal tissues. One such enterprising candidate molecule, pigment epithelium-derived factor (PEDF), has recently been implicated to be involved in control of OS in orthotopic spontaneously metastasising models of the disease, whether administered as recombinant protein, overexpressed or administered as short peptides derived from the parent molecule. Expression of PEDF is inversely proportional to expression of vascular endothelial growth factor (VEGF) at the growth plate cartilage layer of growing bone in both mice and man. PEDF, originally discovered for its potent antiangiogenic activity, is now established as an anticancer factor with multiple mechanisms at its disposal for tumour inhibition. Current efforts are devoted to develop drug delivery systems, such as controlled release nanoparticles, that can be used to progress this potential drug candidate closer towards clinical trials for OS.

Keywords: PEDF, VEGF, osteosarcoma, tumour, angiogenesis, drug delivery, peptide, therapy