Introduction
Platelet-derived growth factor (PDGF) constitutes a family of disulfide-linked dimeric growth factors that promote cell growth and migration by activation of tyrosine kinase PDGFα- and β-receptors (1). PDGFs act predominantly on mesenchymal cells, such as fibroblasts, pericytes, and smooth muscle cells, and are also potent regulators of glial cells. In the context of tumor biology, PDGF isoforms act as autocrine factors for malignant cells, and as stimulators of fibroblasts and pericytes in the tumor stroma. Clinical studies have validated PDGF receptors, expressed on malignant cells or on cells of the tumor stroma, as relevant cancer drug targets (2).
Structure of PDGF and PDGF receptors
PDGF is a family of disulfide-bounded homodimers of homologous A-, B-, C-, and D-polypeptide chains. In addition, the A- and B-chains form a heterodimer PDGF-AB. The two subunits in the dimer are arranged in an anti-parallel manner, creating two symmetric receptor binding epitopes. The PDGF isoforms show sequence similarly to vascular endothelial cell growth factors (VEGFs). In addition, PDGFs, VEGFs, and transforming growth factor-β (TGF-β) show a similar folding with a cystine-knot structure (1).