PLATELET-DERIVED GROWTH-FACTOR - STRUCTURE, FUNCTION AND IMPLICATIONS IN NORMAL AND MALIGNANT-CELL GROWTH

Platelet-derived growth factor (PDGF) is a potent mitogen for a variety of cell types. PDGF is made up as dimers of A and B polypeptide chains which are combined to generate the three isoforms of PDGF (AA, AB, BB). These bind with different specificities and affinities to two types of cell surface receptors (the alpha-receptor and the beta-receptor), both being members of the protein tyrosine kinase family of growth factor receptors. A number of human tumor cell lines, particularly those established from glioma and sarcoma, have been shown to produce PDGF and express the cognate receptor type. In these instances, tumor cell growth may be enhanced by an autocrine receptor activation. In other tumor cell types, where PDGF is produced in the absence of receptor expression, the growth factor may act in a paracrine fashion. This view is supported by our recent finding that human melanoma cells that have been stably transfected with a PDGF B-chain cDNA, elicit a stroma response when transplanted to nude mice.