Anti-EGFR Therapy Combined with Neuromedin B Receptor Blockade Induces the Death of DAOY Medulloblastoma Cells

Overview

Journal Childs Nerv Syst

Specialty Pediatrics

Date 2013 Oct 5

PMID 24092425

Citations 5

Authors

Mariane Jaeger

Carolina Nor

Caroline Brunetto de Farias

Ana Lucia Abujamra

Gilberto Schwartsmann

Algemir Lunardi Brunetto

Rafael Roesler

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: These results provide preliminary evidence that NMBR blockade can potentiate the antitumor effect of anti-EGFR therapy in medulloblastoma.

Citing Articles

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Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy.

Moody T, Lee L, Ramos-Alvarez I, Iordanskaia T, Mantey S, Jensen R Front Endocrinol (Lausanne). 2021; 12:728088.

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Neuropeptide bombesin receptor activation stimulates growth of lung cancer cells through HER3 with a MAPK-dependent mechanism.

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BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells.

Thomaz A, Jaeger M, Buendia M, Bambini-Junior V, Gregianin L, Brunetto A J Mol Neurosci. 2015; 59(3):326-33.

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Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists.

Jaeger M, Ghisleni E, Fratini L, Brunetto A, Gregianin L, Brunetto A Childs Nerv Syst. 2015; 32(1):61-4.

PMID: 26590027 DOI: 10.1007/s00381-015-2963-4.

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