Exogenous Platelet-Derived Growth Factor (PDGF) induces human astrocytoma cell line proliferation

Platelet-derived growth factor receptors (PDGFR) regulate several processes in normal cells including cellular proliferation, differentiation and migration, and are widely expressed in a variety of malignancies. In astrocytoma, PDGF ligand and receptor are often overexpressed and PDGFR activity deregulation has been linked to pathogenesis. The issue of the functional capacity of PDGFR has only occasionally been addressed in glioma cells by measuring the proliferative response induced by exogenous PDGF. In the present study, PDGFR· expression was evaluated in human grade 2 and 4 astrocytoma cell lines and tissue specimens by immunocytochemistry. The receptor responsiveness to exogenous PDGF was determined in astrocytoma cells with an MTT assay. It was found that astrocytoma cells express PDGFR· and respond to PDGF mitogenic action in a grade-dependent manner. The receptor was found to be functional since it induced cell proliferation at different ligand concentrations. We can thus conclude that the proliferative response of human astrocytoma cells is related to their malignancy and receptor status before PDGF stimulation, suggesting a role for PDGFR· inhibitors as blockers of malignant cell proliferation. Tyrosine kinase proteins constitute a large family of molecules that behave as important regulators of intracellular signal transduction pathways (1). Their activities regulate a range of fundamental cellular functions such as proliferation, differentiation, apoptosis, adhesion and migration (2, 3). The deregulation of protein kinase activity has been shown to play a central role in the pathogenesis of many human cancers (4-6). Platelet-derived growth factor (PDGF), a member of this family, is a potent mitogen for mesenchymal cells, playing an essential role in cellular growth, proliferation, differentiation and migration (7). PDGF is produced by a number of cell types, including platelets, endothelial cells, smooth muscle cells, macrophages and glial cells (8), and its function is linked to interaction with specific cell surface receptors. Active PDGF molecules show a dimeric structure that includes A, B, C and D chain homodimers, and AB heterodimer. These isoforms bind two structurally and functionally similar PDGF receptors, denoted · and ‚, with different specificity (9). The ·-receptor binds three different isoforms (PDGF-AA, -AB, -BB) with high and comparable affinity, in the same way as the ‚-receptor