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pmid:30636076

CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas.

Bangbao Tao · Yiqun Ling · Youyou Zhang · Shu Li · Ping Zhou · Xiaoqiang Wang · Bin Li · Zhong Jun · Wenchuan Zhang · Chunyan Xu · Juanhong Shi · Lifeng Wang · Wenhao Zhang · Shiting Li

Molecular oncology · 2019 doi:10.1002/1878-0261.12445

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30636076
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science-record
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sha256:897f68a0624df2ff89aca9410156e02e234b507097432a304256bade77ff763e
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
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2026-11-01T15:40:40Z
updated_at
2026-11-01T22:00:15Z
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paper object · 10 fields
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complete
title
CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas.
doi
10.1002/1878-0261.12445
pmid
30636076
authors array · 14 items
[0]
Bangbao Tao
[1]
Yiqun Ling
[2]
Youyou Zhang
[3]
Shu Li
[4]
Ping Zhou
[5]
Xiaoqiang Wang
[6]
Bin Li
[7]
Zhong Jun
[8]
Wenchuan Zhang
[9]
Chunyan Xu
[10]
Juanhong Shi
[11]
Lifeng Wang
[12]
Wenhao Zhang
[13]
Shiting Li
journal
Molecular oncology
year
2019
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 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 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]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. Thus, CA11/CA10 may represent a potential therapeutic target for the treatment of gliomas.
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The Kaplan–Meier method was used to create survival curves, and the log‐rank test was used to compare survival curves of CA11‐high and CA11‐low expression groups.
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sections[17] "Survival analysis of open‐access datasets" paragraph 2
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The Kaplan–Meier method was used to create survival curves, and the log‐rank test was used to compare survival curves of CA11‐high and CA11‐low expression groups.
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As a repository of brain neoplasia data (REMBRANDT) gliomas, expression data and clinical data were downloaded from REMBRANDT website (http://www.betastasis.com/glioma/rembrandt/kaplan_meier_survival_curve/).
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sections[17] "Survival analysis of open‐access datasets" paragraph 2
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As a repository of brain neoplasia data (REMBRANDT) gliomas, expression data and clinical data were downloaded from REMBRANDT website (http://www.betastasis.com/glioma/rembrandt/kaplan_meier_survival_curve/).
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As a repository of brain neoplasia data (REMBRANDT) gliomas, expression data and clinical data were downloaded from REMBRANDT website (http://www.betastasis.com/glioma/rembrandt/kaplan_meier_survival_curve/).
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Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (gene expression)
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As a repository of brain neoplasia data (REMBRANDT) gliomas, expression data and clinical data were downloaded from REMBRANDT website (http://www.betastasis.com/glioma/rembrandt/kaplan_meier_survival_curve/).
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Molecular subclasses of high-grade glioma: prognosis, disease progression, and neurogenesis
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e glioma (LGG), GSE4271, and GSE42669]. CA11 knockdown promoted cell growth, clone formation, and m
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h, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nud
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in, and 100 mg·mL−1 streptomycin. Cells were cultured in a humidified atmosphere with 5% CO2 at 37 °C
[1]
d in poly‐d‐lysine‐coated dishes and further cultured in Neurobasal supplemented with B27, 0.5 mm glu
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was performed to avoid cross‐contamination. Rat primary cortical neurons were isolated from
[1]
solated from embryonic day 17 Sprague‐Dawley rat brains. Briefly, rat cerebral cortices were
[2]
c day 17 Sprague‐Dawley rat brains. Briefly, rat cerebral cortices were isolated in cold DMEM
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The Kaplan–Meier method was used to create survival curves, and the log‐rank test was used to compare survival curves of CA11‐high and CA11‐low expression groups.
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Complete file
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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 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 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]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. 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