Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment

Extracellular vesicles (EVs) have been shown to transfer various molecules, including functional RNA between cells and this process has been suggested to be particularly relevant in tumor-host interactions. However, data on EV-mediated RNA transfer has been obtained primarily by in vitro experiments...

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Hauptverfasser: Ridder, Kirsten (VerfasserIn) , Umansky, Viktor (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 Mar 2015
In: OncoImmunology
Year: 2015, Jahrgang: 4, Heft: 6
ISSN:2162-402X
DOI:10.1080/2162402X.2015.1008371
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2015.1008371
Verlag, Volltext: https://doi.org/10.1080/2162402X.2015.1008371
Volltext
Verfasserangaben:Kirsten Ridder, Alexandra Sevko, Janina Heide, Maria Dams, Anne-Kathleen Rupp, Jadranka Macas, Julia Starmann, Marc Tjwa, Karl H. Plate, Holger Sültmann, Peter Altevogt, Viktor Umansky, and Stefan Momma

MARC

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520 |a Extracellular vesicles (EVs) have been shown to transfer various molecules, including functional RNA between cells and this process has been suggested to be particularly relevant in tumor-host interactions. However, data on EV-mediated RNA transfer has been obtained primarily by in vitro experiments or involving ex vivo manipulations likely affecting its biology, leaving their physiological relevance unclear. We engineered glioma and carcinoma tumor cells to express Cre recombinase showing their release of EVs containing Cre mRNA in various EV subfractions including exosomes. Transplantation of these genetically modified tumor cells into mice with a Cre reporter background leads to frequent recombination events at the tumor site. In both tumor models the majority of recombined cells are CD45+ leukocytes, predominantly Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs). In addition, multiple lineages of recombined cells can be observed in the glioma model. In the lung carcinoma model, recombined MDSCs display an enhanced immunosuppressive phenotype and an altered miRNA profile compared to their non-recombined counterparts. Cre-lox based tracing of tumor EV RNA transfer in vivo can therefore be used to identify individual target cells in the tumor microenvironment for further mechanistical or functional analysis. 
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