Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo

Extracellular vesicles (EVs) are considered as important mediators of intercellular communication, which carry a diverse repertoire of genetic information between cells. This feature of EVs can be used and improved to advance their therapeutic potential. We have previously shown that genetically eng...

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Bibliographic Details
Published in:Cancer gene therapy 2017-01, Vol.24 (1), p.38-44
Main Authors: Erkan, E P, Senfter, D, Madlener, S, Jungwirth, G, Ströbel, T, Saydam, N, Saydam, O
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Apoptosis - genetics
Biological Transport
Brain cancer
Brain tumors
Care and treatment
Cell Cycle
Cell interactions
Cell Line, Tumor
Cell membranes
Cell Survival - drug effects
Cell Survival - genetics
Cytosine
Cytosine deaminase
Diagnosis
Disease Models, Animal
Drug Delivery Systems
Enhanced green fluorescent protein
Extracellular Vesicles - metabolism
Female
Gene Expression
Gene Transfer Techniques
Genes, Transgenic, Suicide
Genetic diversity
Genetic Engineering
Glioblastoma
Glioblastoma - genetics
Glioblastoma - metabolism
Glioblastoma - pathology
Glioblastoma - therapy
Glioblastoma cells
Glioblastomas
Humans
Mice
Mice, SCID
mRNA
Pentosyltransferases - genetics
Pentosyltransferases - metabolism
Phosphoribosyltransferase
Prodrugs - pharmacology
Proteins
RNA, Messenger
Schwann cells
Suicide
Suicide genes
Tumor Burden - drug effects
Tumor Burden - genetics
Tumor Cells, Cultured
Uracil
Uracil phosphoribosyltransferase
Xenograft Model Antitumor Assays
Xenografts
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Summary:Extracellular vesicles (EVs) are considered as important mediators of intercellular communication, which carry a diverse repertoire of genetic information between cells. This feature of EVs can be used and improved to advance their therapeutic potential. We have previously shown that genetically engineered EVs carrying the suicide gene mRNA and protein-cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT)-inhibited schwannoma tumor growth in vivo. To further examine whether this approach can be applied to other cancer types, we established a subcutaneous xenograft glioblastoma tumor model in mice, as glioblastoma represents the most common primary brain tumor, which is highly aggressive compared with the original schwannoma tumor model. U87-MG glioblastoma cells were implanted into the flanks of nude SCID mice, and the animals were intratumorally injected with the EVs isolated from the cells expressing EGFP or CD-UPRT. After the intraperitoneal administration of the prodrug 5-fluorocytosine, the tumor growth was assessed by regular caliper measurements. Our data revealed that the treatment with the CD-UPRT-enriched EVs significantly reduced the tumor growth in mice. Taken together, our findings suggest that EVs uploaded with therapeutic CD-UPRT mRNA/protein may be a useful tool for glioblastoma treatment.
ISSN:0929-1903
1476-5500
DOI:10.1038/cgt.2016.78