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Oncoimmunology. 2015 Mar 19;4(6):e1008371. eCollection 2015 Jun.

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

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Institute of Neurology (Edinger Institute); Frankfurt University Medical School; German Cancer Consortium (DKTK); German Cancer Research Center (DKFZ) ; Frankfurt, Heidelberg, Germany.
Skin Cancer Unit; German Cancer Research Center; Heidelberg and Department of Dermatology, Venereology and Allergology; University Medical Center Mannheim; Ruprecht-Karl University of Heidelberg ; Mannheim, Heidelberg, Germany.
Tumor Immunology Program; German Cancer Research Center ; Heidelberg, Germany.
Division of Molecular Genome Analysis; German Cancer Research Center ; Heidelberg, Germany.
Laboratory of Vascular Hematology/Angiogenesis; Institute for Transfusion Medicine; Frankfurt University Medical School ; Frankfurt, Germany.


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.


Cre/Lox; GFAP, Glial fibrillary protein; MDSCs; NIH, National Institutes of Health; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate buffered saline; SDS, sodium dodecyl sulfate; carcinoma; exosomes; extracellular vesicles; glioma; immunosuppression; miRNA

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