Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Open accessAbstract
Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.
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mRNA profiling of serum-derived EV contents can discriminate between healthy and glioblastoma-bearing patients, and IDH-1, EGFRvIII, and c-myc alterations have been detected in EVs from glioblastoma or medulloblastoma samples.
“For example, mRNA profiling of serum derived EV contents can discriminate between healthy and glioblastoma bearing patients [118]. IDH-1 (isocitrate dehydrogenase 1) transcripts have been detected from EVs isolated from the blood of glioblastoma bearing patients using immunoisolations of EVs targeting CD63 [119].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [1]
In the paper’s biomarker results (page not available), EGFRvIII mRNA was detected in serum microvesicles from 7 of 25 glioblastoma patients and in none of 30 normal control sera. That supports a distinction for this specific marker, but not the broader claim that mRNA profiling of serum-derived EVs can discriminate glioblastoma-bearing patients from healthy people generally. The IDH-1 sentence is attached to a different citation and is not assessed here. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe contents of released extracellular vesicles mirror aspects of the secreting cell.
“the contents of the vesicles released mirror aspects of the secreting cell. [1]”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [1]
Extracellular vesicles can transfer RNAs such as non-coding RNAs from one cell to another and thereby contribute to inter-cellular communication.
“Recent studies have confirmed that EV can transfer RNAs such as ncRNAs from one cell to another and thereby contribute to important roles in inter-cellular communication (3–9).”
From Analysis of Extracellular RNA by Digital PCR (2014) · cites this paper as [5]
In GBM, communication between tumor cells and the microenvironment has a big impact on tumor progression.
“In GBM, similar to other cancer types, the communication between tumor cells and its microenvironment has a big impact on tumor progression; and hence it provided a new approach for cancer treatment (3, 4).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [3]
ELV preparations from various cell types contain distinctive repertoires of RNA populations including transcripts and non-coding RNAs.
“ELV preparations from various cell types have demonstrated that they contain distinctive repertoires of RNA populations including transcripts (Valadi et al., 2007; Skog et al., 2008) and non-coding RNAs”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Skog et al., 2008
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- Authors
- Skog, J., Würdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T., Carter, B. S., Krichevsky, A. M., & Breakefield, X. O.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Breakefield, Xandra O.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2008-11-16
- Volume
- 10
- Issue
- 12
- Pages
- 1470-1476
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3423894
- OpenAlex
- W2030701238
- Cited by
- 5,001
- References
- 38
- Citations by year
- 2026: 136 · 2025: 207 · 2024: 279 · 2023: 282 · 2022: 337 · 2021: 427 · 2020: 426 · 2019: 368 · 2018: 384 · 2017: 349 · 2016: 357 · 2015: 336 · 2014: 301 · 2013: 272 · 2012: 230
- FWCI
- 42.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Cancer Institute (CA -69246, P01CA069246, P50CA086355, CA 86355)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- glioblastoma, microvesicles, exosomes, extracellular vesicles, RNA delivery, microRNA, EGFRvIII, miR-21, angiogenic factors, brain microvascular endothelial cells, endothelial tube formation, tumor cell proliferation, serum biomarkers, liquid biopsy
- MeSH terms
- Glioblastoma, Humans, Neoplasm Proteins, Neovascularization, Pathologic, RNA, Biomarkers, Tumor, RNA Transport, Endothelial Cells, Angiogenesis Inducing Agents, Cell Proliferation, Exosomes
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