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Function of extracellular vesicle-associated miRNAs in metastasis

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Abstract

Extracellular RNA (exRNA) is functionally transferrable from donor to recipient cells and is protected from RNAses by electrostatic interactions with proteins or by membrane encapsulation. In addition to bioactive RNA, extracellular vesicles (EVs) contain intraluminal and membrane-associated proteins. The cellular context and fitness affect the composition of EVs and thus the outcome of the communication between the EV-producer and recipient cells. Adaptive communication through EVs is particularly important between cancer cells and their local and distant environment and drives life-threatening metastatic progression. Small noncoding RNAs (miRNAs) have been reported in EV isolations and play a role in local invasion, angiogenesis, immune modulation, metastatic niche preparation, colonization and dormancy. The metastasis-related functions attributed to EV-associated miRNAs are currently increasing exponentially in the scientific literature. We must be aware that the correct and efficient separation of non-vesicular entities (soluble proteins, RNA-protein complexes and RNA-lipoprotein complexes) from EVs is necessary to determine the true contribution of EVs in any experiment that describes the molecular content or the functional consequences of the isolated material.

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    Authors and Affiliations

    1. Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium

      Bert Dhondt, Quentin Rousseau, Olivier De Wever & An Hendrix

    2. Department of Uro-Gynaecology, Ghent University Hospital, Ghent, Belgium

      Bert Dhondt

    3. Cancer Research Institute Ghent (CRIG), Ghent, Belgium

      Bert Dhondt, Quentin Rousseau, Olivier De Wever & An Hendrix

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    1. Bert Dhondt
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    2. Quentin Rousseau
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    Correspondence to An Hendrix.

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    Bert Dhondt and Quentin Rousseau contributed equally to this work.

    This work was supported by the Fund for Scientific Spearheads of Ghent University Hospital, Concerted Research Actions from Ghent University, Stichting tegen Kanker, Vlaamse Liga tegen Kanker, a postdoctoral grant (to A.H.) from the Fund for Scientific Research-Flanders and funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013/ under REA grant agreement no. [316610] (to Q.R.).

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    Dhondt, B., Rousseau, Q., De Wever, O. et al. Function of extracellular vesicle-associated miRNAs in metastasis. Cell Tissue Res 365, 621–641 (2016). https://doi.org/10.1007/s00441-016-2430-x

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