Platelet-derived growth factor (PDGF) receptor (PDGFR) expression correlates 
with metastatic medulloblastoma. PDGF stimulation of medulloblastoma cells 
phosphorylates extracellular signal-regulated kinase (ERK) and promotes 
migration. We sought to determine whether blocking PDGFR activity effectively 
inhibits signaling required for medulloblastoma cell migration and invasion. 
DAOY and D556 human medulloblastoma cells were treated with imatinib mesylate 
(Gleevec), a PDGFR tyrosine kinase inhibitor, or transfected with small 
interfering RNA (siRNA) to PDGFRB to test the effects of blocking PDGFR 
phosphorylation and expression, respectively. PDGFR cell signaling, migration, 
invasion, survival, and proliferation following PDGF-BB stimulation, with and 
without PDGFR inhibition, were measured. PDGF-BB treatment of cells increased 
PDGFRB, Akt and ERK phosphorylation, and transactivated epidermal growth factor 
receptor (EGFR), which correlated with enhanced migration, survival, and 
proliferation. Imatinib (1 μmol/L) treatment of DAOY and D556 cells inhibited 
PDGF-BB- and serum-mediated migration and invasion at 24 and 48 h, respectively, 
and concomitantly inhibited PDGF-BB activation of PDGFRB, Akt, and ERK but 
increased PTEN expression and activity. Imatinib treatment also induced DAOY 
cell apoptosis at 72 h and inhibited DAOY and D556 cell proliferation at 48 h. 
siRNA silencing of PDGFRB similarly inhibited signaling, migration, and survival 
and both siRNA and imatinib treatment inhibited PDGF-BB-mediated EGFR 
transactivation, indicating that the effects of imatinib treatment are specific 
to PDGFRB target inhibition. These results indicate that PDGFRB tyrosine kinase 
activity is critical for migration and invasion of medulloblastoma cells 
possibly by transactivating EGFR; thus, imatinib may represent an important 
novel therapeutic agent for the treatment of medulloblastoma.