The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential

Abstract

The potent actions of pigment epithelium-derived factor (PEDF) on tumour-associated cells, and its extracellular localization and secretion, stimulated research on this multifunctional serpin. Such studies have identified several PEDF receptors and downstream signalling pathways. Known cellular PEDF responses have expanded from the initial discovery that PEDF induces retinoblastoma cell differentiation to its anti-angiogenic, antitumorigenic and antimetastatic properties. Although the diversity of PEDF activities seems to be complex, they are consistent with the varied mechanisms that regulate this multimodal factor. If PEDF is to be used for cancer management, a deeper appreciation of its many functions and mechanisms of action is needed.

Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia

“…Several studies showed that PEDF level declines with age, and suggested that this decline may play a key role in the development of angiogenic-related pathologies (18). Moreover, it was shown that decrease in PEDF expression is one of the mechanisms that promote tumor growth (19), suggesting PEDF as an anticancer therapy (20,21). We have recently characterized the expression and regulation of PEDF in human and rodent premenopausal endometrium, indicating that PEDF is dynamically expressed in mice endometrium throughout the estrous cycle, in reciprocity to VEGF, and that the balance between the two is regulated by estrogen and progestrone (22,23).…”

Pigment epithelial-derived factor gene loaded novel COOH-PEG-PLGA-COOH nanoparticles promoted tumor suppression by systemic administration

“…The reason might be that the PEDF which successfully expressed in the tumor tissue increased the levels of p53 and BAX and concomitantly inhibited BCL-2. 7 This observation indicated that the growth inhibitory effect of C26 tumors was also associated with the apoptosis of C26 cells in vivo. Considering these results, D-NPs could successfully delivery PEDF gene into the tumor cells and would be a promising approach for antitumor therapy.…”

“…[2][3][4][5] Pigment epithelium-derived factor (PEDF), as a member of the serine protease inhibitor (serpin) superfamily, has been reported to be one of the most potent inhibitors of angiogenesis. [6][7][8] PEDF is a 50 kDa secreted glycoprotein that belongs to a group of proteins having a common three-dimensional structure. 7 Compared with the direct protein administration, PEDF gene might be cheaper and achieve higher antitumor efficacy due to easier access to tumor tissue.…”

“…[6][7][8] PEDF is a 50 kDa secreted glycoprotein that belongs to a group of proteins having a common three-dimensional structure. 7 Compared with the direct protein administration, PEDF gene might be cheaper and achieve higher antitumor efficacy due to easier access to tumor tissue. Gene therapy, transferring therapeutic genes to tumor cells using diverse delivery vehicles, has been developed as a potential treatment modality for cancers.…”

Pigment epithelium-derived factor has a role in the progression of papillary thyroid carcinoma by affecting the HIF1α-VEGF signaling pathway

“…PEDF has numerous biological functions, including differentiating activity, neurite outgrowth, survival activity, anti-apoptosis and anti-angiogenic activities and the induction of cell death (13)(14)(15)(16)(17)(18)(19). The anticancer role of PEDF has yet to be elucidated; however, previous studies have suggested various roles for PEDF in inhibiting cancer progression.…”