CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas
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‐relat...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-05-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12445 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846150612407812096 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Bangbao Tao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-85099edbeeab497fbe1aa3567b7d6c86 |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-85099edbeeab497fbe1aa3567b7d6c862024-11-28T11:26:19ZengWileyMolecular Oncology1574-78911878-02612019-05-011351018103210.1002/1878-0261.12445CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomasBangbao Tao0Yiqun Ling1Youyou Zhang2Shu Li3Ping Zhou4Xiaoqiang Wang5Bin Li6Zhong Jun7Wenchuan Zhang8Chunyan Xu9Juanhong Shi10Lifeng Wang11Wenhao Zhang12Shiting Li13Department of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Nutrition Fudan University Shanghai Cancer Center ChinaDepartment of Endocrinology The First Hospital of Taizhou Wenzhou Medical University Taizhou ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Pathology Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Pathology Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Pathology Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Hematology Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaDepartment of Neurosurgery Xinhua Hospital Shanghai Jiaotong University School of Medicine ChinaRecent 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.https://doi.org/10.1002/1878-0261.12445CA10CA11gliomasmicroenvironmentneuroligin‐3neurons |
| spellingShingle | 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 CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas Molecular Oncology CA10 CA11 gliomas microenvironment neuroligin‐3 neurons |
| title | CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas |
| title_full | CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas |
| title_fullStr | CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas |
| title_full_unstemmed | CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas |
| title_short | CA10 and CA11 negatively regulate neuronal activity‐dependent growth of gliomas |
| title_sort | ca10 and ca11 negatively regulate neuronal activity dependent growth of gliomas |
| topic | CA10 CA11 gliomas microenvironment neuroligin‐3 neurons |
| url | https://doi.org/10.1002/1878-0261.12445 |
| work_keys_str_mv | AT bangbaotao ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT yiqunling ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT youyouzhang ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT shuli ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT pingzhou ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT xiaoqiangwang ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT binli ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT zhongjun ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT wenchuanzhang ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT chunyanxu ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT juanhongshi ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT lifengwang ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT wenhaozhang ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas AT shitingli ca10andca11negativelyregulateneuronalactivitydependentgrowthofgliomas |