PLATELET-DERIVED GROWTH-FACTOR IN HUMAN GLIOMA

Platelet-derived growth factor (PDGF) is a 30 kDa protein consisting o f disulfide-bonded dimers of A- and B-chains. PDGF receptors are of tw o types, alpha- and beta-receptors, which are members of the protein-t yrosine kinase family of receptors. The receptors are activated by lig and-induced dimerization, whereby the receptors become phosphorylated on tyrosine residues. These form attachment sites for signalling molec ules, which inter alia activate the Ras Raf pathway. PDGF has importan t functions in development and is required for a proper timing of olig odendrocyte differentiation. The v-sis oncogene of simian sarcoma viru s (SSV) is a retroviral homolog of the B-chain gene, and induces trans formation by an autocrine activation of PDGF receptors at the cell sur face. SSV induces malignant glioma in experimental animals, suggesting a role for autocrine PDGF in glioma development. PDGF and PDGF recept ors are frequently coexpressed in human glioma cell lines. Specific an d nonspecific PDGF antagonists block the growth of some glioma cell li nes in vitro and in vivo, suggesting that autocrine PDGF is involved i n transformation and tumorigenesis. In situ studies of human gliomas s how overexpression of alpha-receptors in glioma cells of high-grade tu mors. In a few cases, overexpression is caused by receptor amplificati on. Since high-grade glioma cells also express the PDGF A-chain, an au tocrine activation of the a-receptor may drive the proliferation of gl ioma cells in vivo. (C) 1995 Wiley-Liss, Inc.