Perspectives Platelet-derived Growth Factor Structure, Function, and Roles

Polypeptide growth factors regulate the proliferation of cells in culture alone or in concert with other mitogens by inducing DNA synthesis and cell division in specific target cells. The mechanisms of action and the in vivo functions of these polypeptide growth factors are not known. It seems likely that growth factors have some role in cell development, differentia-tion, and tissue repair. Of the known growth factors, epidermal growth factor (EGF), ' the platelet-derived growth factor (PDGF), and nerve growth factor are best defined. Each interacts with target cells through specific cell-surface receptors, leading to DNA synthesis, cell proliferation, and morphological and biochemical changes which resemble those characteristic of cells transformed by acute retroviruses (1-5). Malignant transformed cells also synthesize and secrete polypeptide growth factors which may stimulate autonomous cellular proliferation by an autocrine mechanism (6). In this article, we will sum-marize results of recent studies on the structure and biology of one well-characterized growth factor, PDGF, and attempt to relate how PDGF and perhaps PDGF-like molecules may play important roles in malignant transformation and cell growth of virus-transformed cells. Origins ofPDGF Platelets do not bind to intact endothelium. PDGF is contained in alpha granules of platelets and is released only during blood clotting or when platelets adhere at sites of blood vessel injury. Secretion of platelet contents can be initiated by exposure of platelets to foreign surfaces such as subendothelial basement membrane or collagen (7-9). PDGF may serve to promote wound healing since it is the most potent mitogen in serum for cells of mesenchymal origins, including fibroblasts, glial cells, and smooth muscle cells (10, 11). Cells ordinarily ar