Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, are extracellular nanovesicles released by most cells. EVs play essential roles in intercellular communication via the transport of a large variety of lipids, proteins, and nucleic acids to recipient cells. Nucleic acids are the most commonly found molecules inside EVs, and due to their small size, microRNAs and other small RNAs are the most abundant nucleic acids. However, longer molecules, such as messenger RNAs (mRNAs), have also been found. mRNAs encapsulated within EVs have been shown to be transferred to recipient cells and translated into proteins, altering the behavior of the cells. Secretion of EVs is maintained not only through multiple normal physiological conditions but also during aberrant pathological conditions, including cancer. Recently, the mRNAs carried by EVs in cancer have attracted great interest due to their broad roles in tumor progression and microenvironmental remodeling. This review focuses on the biological functions driven by mRNAs carried in EVs in cancer, which include supporting tumor progression by activating cancer cell growth, migration, and invasion; inducing microenvironmental remodeling via hypoxia, angiogenesis, and immunosuppression; and promoting modulation of the microenvironment at distant sites for the generation of a premetastatic niche, collectively inducing metastasis. Furthermore, we describe the potential use of mRNAs carried by EVs as a noninvasive diagnostic tool and novel therapeutic approach.

Highlights

  • Intercellular communication is essential for the appropriate performance of multicellular organisms

  • The new vasculature supplies nutrients and oxygen to cancer cells and provides an escape route for tumor cell migration and metastasis. An example of this process is a population of renal carcinoma cells that were found to secrete Extracellular vesicles (EVs) containing the proangiogenic VEGF, FGF2, Angiopoietin1, Ephrin A3, MMP2, and MMP9 messenger RNAs (mRNAs), which promoted in vivo angiogenesis and lung metastasis (Grange et al, 2011)

  • Use of Non-pathological mRNAs Carried by EVs Because EVs are taken up by cancer cells, an alternative therapeutic approach is to reengineer naturally derived EVs for targeted gene therapy and drug delivery (Arslan et al, 2013; Katsuda et al, 2013; Ohno et al, 2013; Mao et al, 2018)

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Summary

Introduction

Intercellular communication is essential for the appropriate performance of multicellular organisms. Cancer cells constitutively secrete EVs in Proposal of the effect of mRNA carried by EVs. ES-derived EVs containing high levels of Wnt3 induced stemness-related gene expression in recipient cells.

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