Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway
Abstract Background Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-021-00760-9 |
| _version_ | 1828138153995665408 |
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| author | Jiabin Pan Shiyang Sheng Ling Ye Xiaonan Xu Yizhao Ma Xuanran Feng Lisha Qiu Zhaohuan Fan Yi Wang Xiaohuan Xia Jialin C. Zheng |
| author_facet | Jiabin Pan Shiyang Sheng Ling Ye Xiaonan Xu Yizhao Ma Xuanran Feng Lisha Qiu Zhaohuan Fan Yi Wang Xiaohuan Xia Jialin C. Zheng |
| author_sort | Jiabin Pan |
| collection | DOAJ |
| description | Abstract Background Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown. Methods We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs. Results We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs. Conclusion Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. Video Abstract |
| first_indexed | 2024-04-11T18:31:34Z |
| format | Article |
| id | doaj.art-fbd35653dcf942369cd200667451226a |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-11T18:31:34Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-fbd35653dcf942369cd200667451226a2022-12-22T04:09:26ZengBMCCell Communication and Signaling1478-811X2022-01-0120111610.1186/s12964-021-00760-9Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathwayJiabin Pan0Shiyang Sheng1Ling Ye2Xiaonan Xu3Yizhao Ma4Xuanran Feng5Lisha Qiu6Zhaohuan Fan7Yi Wang8Xiaohuan Xia9Jialin C. Zheng10Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated to Tongji University School of MedicineAbstract Background Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown. Methods We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs. Results We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs. Conclusion Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. Video Abstracthttps://doi.org/10.1186/s12964-021-00760-9GlioblastomaExtracellular vesiclesNeural progenitor cellsProliferationMigrationPI3K |
| spellingShingle | Jiabin Pan Shiyang Sheng Ling Ye Xiaonan Xu Yizhao Ma Xuanran Feng Lisha Qiu Zhaohuan Fan Yi Wang Xiaohuan Xia Jialin C. Zheng Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway Cell Communication and Signaling Glioblastoma Extracellular vesicles Neural progenitor cells Proliferation Migration PI3K |
| title | Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway |
| title_full | Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway |
| title_fullStr | Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway |
| title_full_unstemmed | Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway |
| title_short | Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway |
| title_sort | extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via pi3k akt pathway |
| topic | Glioblastoma Extracellular vesicles Neural progenitor cells Proliferation Migration PI3K |
| url | https://doi.org/10.1186/s12964-021-00760-9 |
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