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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 utilized two classic glioblastoma cell lines, U87- and A172, and collected EVs in the culture medium of those two lines. Mouse NPCs (mNPCs) were co-cultured with U87- or A172-derived EVs. EVs-treated mNPCs’ prolifeartion and migration were examined. Proteomic analysis and western-blot were utilized to identify the underlying mechanisms of glioblastoma EVs-induced alterations in mNPCs.
Results
We show that glioblastoma cell lines U87- and A172-derived EVs dramatically promoted NPCs proliferation and migration. Mechanistic studies identify that EVs achieve their functions via activating PI3K-Akt-mTOR pathway in recipient cells. Inhibiting PI3K-Akt reversed the elevated prolfieration and migration of glioblastoma 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.
Keywords
Glioblastoma, Extracellular vesicles, Neural progenitor cells, Proliferation, Migration, PI3K, Akt
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View the published article at Cell Communication and Signaling.
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See the published version of this preprint at Cell Communication and Signaling.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cell Communication and Signaling.
Version 1
Posted 28 Jan, 2021
No community comments so far
Editor assigned
On 20 Jan, 2021
Submission checks complete
On 20 Jan, 2021
Editor invited
On 20 Jan, 2021
First submitted
On 18 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cell Communication and Signaling
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cell Communication and Signaling.
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 utilized two classic glioblastoma cell lines, U87- and A172, and collected EVs in the culture medium of those two lines. Mouse NPCs (mNPCs) were co-cultured with U87- or A172-derived EVs. EVs-treated mNPCs’ prolifeartion and migration were examined. Proteomic analysis and western-blot were utilized to identify the underlying mechanisms of glioblastoma EVs-induced alterations in mNPCs.
Results
We show that glioblastoma cell lines U87- and A172-derived EVs dramatically promoted NPCs proliferation and migration. Mechanistic studies identify that EVs achieve their functions via activating PI3K-Akt-mTOR pathway in recipient cells. Inhibiting PI3K-Akt reversed the elevated prolfieration and migration of glioblastoma 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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