Diagnostic, Therapeutic and Prognostic Potential of Pigment Epithelium-Derived Factor in Cancer

Abstract

This review highlights recent findings on the versatile serpin protein, pigment epithelium-derived factor (PEDF), in relation to cancer diagnosis, treatment and prognosis. PEDF was initially discovered in the eye but has since been reported to be relevant to various biological roles in the body, and when awry, to clinically lead to various disease states such as neoplasia. At the preclinical stage, potent effects have been reported in studies focussing on apoptosis, metastasis, oxidative stress, immune stimulation and metabolism. Apart from full-length proteins, short peptides based on PEDF have shown promise against cancer. For diagnosis and prognosis, PEDF levels in tumour specimens or in circulation have the potential to serve as biomarkers, most probably in combination with other biomarkers of cancer initiation and progression. Lastly, this review discusses the growing list of studies that point out the perceived pro-cancerous effects of PEDF, though this is clearly outweighed by the anticancer publications. Thus, this review provides a comprehensive and balanced listing of the oncological studies associated with this protein to date, drawing conclusions on whether this potent antiangiogenic protein and its peptides can be used in the future for better cancer treatment, especially against metastasis.

Keywords: PEDF; biomarker; cancer; metabolism; metastasis; oxidative stress.

Figure 1

PEDF-based 25-mer peptides. Two unique short 25-mer peptides (A) residues 78-102 (78 VLLSPLSVATALSALSLGAEQRTES102), and (B) residues 90-114 (90 SALSLGAEQRTESIIHRALYYDLIS 114), inhibit osteosarcoma growth and metastasis and like PEDF, support bone formation. In comparison, two other major PEDF peptides are the 34mer sequence (Asp44-Asn77), and the 44mer sequence (Val78–Thr121). Advantages of using such short peptides rather than parent protein: versatility may be problematic as parent protein has diverse (and perhaps conflicting) activities, the full-length protein is expensive, peptides should be more stable, several labs have designed short length peptides which show similar activity to full length protein, and peptides allow a degree of targeted activity.

Figure 2

Summary of PEDF relationships to cancer and major markers uncovered. The figure summarises the types of tumours where PEDF is implicated in metastasis, markers of metastasis that are engaged by PEDF, apoptotic markers affected by PEDF in cancer cells, oxidative stress markers activated by PEDF in cancer cells, and correlation of PEDF at the protein level with various types of cancers found clinically.