The Role that PDGF and PDGFR play in GBM Angiogenesis

(Nature Reviews, 2002)

The platelet derived growth factor (PDGF) targets endothelial cells, vascular smooth muscle cells, osteoblasts, glia, and neurons resulting in proliferation, resistance to apoptosis, tumor growth, and angiogenesis (Nobuo et al, 2006).

The isoforms of PDGF are activated by dimerization (Fredrikkson et al, 2004). Dimerized ligands bind to tyrosine trans receptor subunits inducing dimerization (Roskoski, 2007). Dimerization leads to trans-auto phosphorylation by intracellular tyrosine domains which activate signal transduction pathways promoting downstream gene transcription activity (Choudhury et al, 2010).

PDGFB and PDGF-β are overexpressed in hyperplastic tumor endothelial cells (Hermansson et al, 1988). The expression of these proteins leads to increased transcription and secretion of VEGF by endothelial cells via the PI3K pathway (Karar et al, 2011).