Format

Send to

Choose Destination
J Mol Neurosci. 2016 Jul;59(3):326-33. doi: 10.1007/s12031-015-0689-0. Epub 2015 Nov 27.

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

Author information

1
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
2
Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil.
3
Laboratory of Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 21040-360, Rio de Janeiro, RJ, Brazil.
4
Department of Pediatrics, Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
5
Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil.
6
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil. rroesler@terra.com.br.
7
Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil. rroesler@terra.com.br.
8
Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil. rroesler@terra.com.br.

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.

KEYWORDS:

Brain tumor; Brain-derived neurotrophic factor; Childhood cancer; Medulloblastoma; TrkB

PMID:
26614346
DOI:
10.1007/s12031-015-0689-0
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center