Biology of platelet-derived growth factor and its involvement in disease.

Platelet-derived growth factor (PDGF) is mainly believed to be an important mitogen for connective tissue, especially for fibroblasts that serve in wound healing. However, PDGF also has important roles during embryonal development, and its overexpression has been linked to different types of fibrotic disorders and malignancies. Platelet-derived growth factor is synthesized by many different cell types, and its expression is broad. Its synthesis is in response to external stimuli, such as exposure to low oxygen tension, thrombin, or stimulation by other cytokines and growth factors. In addition, PDGF may function in autocrine stimulation of tumor cells, regulation of interstitial fluid pressure, and angiogenesis. Recently, several drugs were developed that are potent inhibitors of the tyrosine kinase activity of PDGF receptors. Thus, it is important to understand the physiology of PDGF and its receptors and the role of PDGF in different diseases. This review summarizes the physiologic activity of PDGF, the expression of PDGF during embryonal development, and the roles of PDGF expression in nonmalignant disease and in different tumors.