Platelet-derived growth factor as a mediator of normal and neoplastic cell proliferation

Abstract

Human platelet-derived growth factor is the major mitogen in serum for connective-tissue-derived cells in culture. The factor is 30,000 mol. wt protein composed of two disulphide-linked polypeptide chains, named A and B. The B-chain is virtually identical to part of the transforming protein of simian sarcoma virus (SSV), implying that SSV-transformation is mediated by a PDGF-like growth factor. This notion is supported by the finding that specific as well as nonspecific inhibitors of PDGF-action (PDGF antibodies and suramin, respectively) are efficient inhibitors of SSV-transformation and revert the transformed phenotype of SSV-transformed cells. Expression of the genes encoding the PDGF subunits and production of PDGF-like growth factors is a common feature of human sarcoma cell lines, suggesting a role of PDGF in the pathogenesis of sarcomas, although direct support in favor of this notion is lacking. An involvement of PDGF in autocrine and paracrine stimulation of normal cell growth is suggested by the finding that responsive (arterial smooth muscle cells and placental cytotrophoblasts) as well as nonresponsive (endothelial cells and macrophages) cells produce PDGF-like growth factors. In conclusion, PDGF-like growth factors may be widely implicated in normal as well as neoplastic growth processes.