Pigment Epithelium-Derived Factor Involvement in Angiogenesis and Cancer Biology

Pigment epithelium-derived factor (PEDF) is a 50 kDa secreted glycoprotein of the serpin family, notable for its potent anti-angiogenic, neurotrophic and tumour-suppressive activities. Originally identified in retinal pigment epithelium, PEDF has since been shown to modulate vascular growth by counteracting pro-angiogenic stimuli, stabilising endothelial junctions and promoting a quiescent phenotype in microvascular networks. In cancer biology PEDF exerts indirect effects on the tumour microenvironment by inhibiting new vessel formation, reducing vascular permeability and limiting metastasis, while direct actions include induction of apoptosis, suppression of tumour cell proliferation and modulation of immune cell infiltration. Molecularly, PEDF interacts with multiple high-affinity receptors and coreceptors on endothelial and tumour cells, triggering downstream pathways such as PI3K-AKT-mTOR, MAPK/ERK and regulated intramembrane proteolysis of VEGFR-1. The balance between PEDF and vascular endothelial growth factor (VEGF) levels constitutes a critical determinant of angiogenic switch in both physiological and pathological contexts. Preclinical studies highlight PEDF’s capacity to synergise with chemotherapeutics, protect normal tissue integrity and normalise tumour vasculature. Ongoing research focuses on delivery systems, receptor agonists and the dual modulation of metabolic and immune checkpoints to harness PEDF’s pleiotropic properties for anti-angiogenic and anti-tumour therapy.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Pigment Epithelium-Derived Factor Involvement in Angiogenesis and Cancer Biology publication trend

The graph below shows the total number of articles in pigment epithelium-derived factor involvement in angiogenesis and cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: formation of new blood vessels from pre-existing vasculature.

Pigment Epithelium-Derived Factor (PEDF): a secreted serpin family glycoprotein with anti-angiogenic, neurotrophic and anti-tumour functions.

VEGFR-1: vascular endothelial growth factor receptor 1; a receptor tyrosine kinase central to angiogenic signalling.

Proteolytic cleavage: enzymatic hydrolysis of peptide bonds resulting in fragmentation of a protein.

PLXDC1/2: plexin domain-containing transmembrane receptors that mediate PEDF signalling.

Intramembrane proteolysis: regulated cleavage of a membrane protein’s transmembrane segment.

Metastasis: dissemination of cancer cells from the primary site to distant organs.

References

1. The Various Roles of PEDF in Cancer. Cancers (2024).
2. Pigment Epithelium-derived Factor Inhibits Angiogenesis via Regulated Intracellular Proteolysis of Vascular Endothelial Growth Factor Receptor 1*. Journal of Biological Chemistry (2005).
3. Pigment Epithelium-derived Factor Behaves Like a Noninhibitory Serpin NEUROTROPHIC ACTIVITY DOES NOT REQUIRE THE SERPIN REACTIVE LOOP (∗). Journal of Biological Chemistry (1995).
4. Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF. eLife (2014).