Antibodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus

Abstract

A clue to the molecular mechanism of neoplastic transformation was provided by the finding of a near identity in amino-acid sequence between the platelet-derived growth factor (PDGF) B-chain and a region in the transforming protein, p28sis, of simian sarcoma virus (SSV), an agent that causes sarcomas and gliomas in experimental animals. This finding infers a direct link between the molecular biology of normal mitogenesis and oncogenesis since it suggests that the transforming activity of SSV is caused by a growth factor. Although PDGF agonist activity has been isolated from conditioned medium of SSV-transformed cells, it is not clear whether infection of responsive cells by SSV leads solely to autocrine stimulation of growth by a secreted PDGF-like factor or whether other, possibly intracellular, activities of p28sis or its processed products contribute to the transformation. To distinguish between these possibilities, we have studied the effect of anti-PDGF antibodies on acute SSV-transformation, and report here that these antibodies inhibit both proliferation and SSV-induced morphological changes in human diploid fibroblasts.