Anti-EGFR therapy combined with neuromedin B receptor blockade induces the death of DAOY medulloblastoma cells

Abstract

Medulloblastoma is the most common malignant childhood brain tumor for which the development of new molecularly targeted therapies is needed. Novel therapeutic targets under investigation include growth factor receptors. Here, we show that the combined inhibition of the epidermal growth factor receptor (EGFR) and neuromedin B receptor (NMBR, BB1) results in increased cell death in human medulloblastoma cell lines. DAOY and D283 human medulloblastoma cells were treated with human recombinant neuromedin B (NMB, an NMBR agonist), the NMBR antagonist BIM-23127, the anti-EGFR monoclonal antibody cetuximab, or BIM-23127 combined with cetuximab. Cell death was examined with trypan blue cell counting. Both cell lines expressed mRNA for EGFR, NMB, and NMBR detected by reverse transcriptase polymerase chain reaction. Cetuximab at 10 μg/ml significantly reduced the number of DAOY cells, but did not affect D283 cells. NMB and BIM-23127 did not change cell number when used alone. However, cetuximab, at a dose that did not have an effect by itself, was able to reduce the number of DAOY cells when combined with BIM-23127. These results provide preliminary evidence that NMBR blockade can potentiate the antitumor effect of anti-EGFR therapy in medulloblastoma.