In:
Molecular Oncology, Wiley, Vol. 13, No. 5 ( 2019-05), p. 1018-1032
Abstract:
Recent studies have revealed that neurons can promote glioma growth through activity‐dependent secretion of neurotrophins, especially neuroligin‐3. It has therefore been suggested that blocking neuron‐derived neurotrophins may serve as a therapeutic intervention for gliomas. Carbonic anhydrase‐related proteins 11 and 10 ( CA 11 and CA 10) are secreted synaptic proteins which function as neurexin ligands, and the gene‐encoding CA 11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA 11/ CA 10 might participate in the neuronal activity‐dependent regulation of glioma growth. In this study, we report that CA 11 secreted by depolarized cultured neurons within conditioned medium ( CM ) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA 11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA 11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA 11 expression of gliomas was associated with short survival in four independent datasets [repository of brain neoplasia data ( REMBRANDT ), The Cancer Genome Atlas ( TCGA ) lower grade glioma (LGG), GSE4271 , and GSE42669 ]. CA 11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA 10 and CA 10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA 10 expression was associated with short survival in REMBRANDT , TCGA LGG , and GEO GSE4271 datasets. Our results suggest that CA 11 and CA 10 negatively regulate neuronal activity‐dependent glioma growth and inhibit glioma aggression. Thus, CA 11/ CA 10 may represent a potential therapeutic target for the treatment of gliomas.
Type of Medium:
Online Resource
ISSN:
1574-7891
,
1878-0261
DOI:
10.1002/mol2.2019.13.issue-5
DOI:
10.1002/1878-0261.12445
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2322586-5
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