Platelet-derived growth factor in human malignancy.
Platelet-derived growth factor (PDGF) was first implicated in the process of transformation when one of its peptide chains was found to be homologous to the viral sis oncogene (v-sis). Since that time, there have been multiple demonstrations of the transforming activity of v-sis in fibroblasts. Because of the near identity of the v-sis protein with the PDGF B chain, v-sis is thought to transform through an autocrine stimulatory mechanism of cell growth. Consistent with this view are studies which demonstrate inhibition of v-sis-mediated transformation by anti-PDGF antibodies. Expression of the cellular sis gene (c-sis) and its receptors, and secretion of PDGF-like factors have been demonstrated in many types of human malignant cells. Nevertheless, a causative role for c-sis in inducing or maintaining the transformed phenotype in human malignancies remains to be established. There are significant differences in structure between v-sis and c-sis. Studies of transforming ability have yielded conflicting results in transfection models, depending on the transfected vector and target cell type utilized. While there is compelling evidence for the involvement of PDGF in an autocrine growth mechanism in transformed fibroblasts, the evidence in human epithelial tumor types is less convincing because PDGF receptors are usually not detectable on the cell surface. The recent demonstration of intracellular co-localization of active PDGF precursors and PDGF receptors, however, supports the existence of an internal autocrine pathway independent of PDGF secretion. Further investigation of such a mechanism in de novo human malignancies is warranted to establish the role of PDGF in the development of these neoplasms.
Silver
B J
BJ
Department of Medicine, Case Western Reserve University, Cleveland, OH.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor