Transfer of microRNAs by extracellular membrane microvesicles: a nascent crosstalk model in tumor pathogenesis, especially tumor cell-microenvironment interactions.

Li Zhang,Meng Chen,Biao Dong,Ling Pan,C Alexander Valencia,Pu-Jun Guan

doi:10.1186/s13045-015-0111-y

Abstract

Anticancer treatments aiming at killing malignant cells have been applied for decades but have been unsuccessful at curing the disease. The modern concept of tumor microenvironment, especially angiogenesis, suggests that the tumor is not only composed of malignant cells, but also consists of other groups of cells that work together. Recently, genetic message transfer has been revealed between tumor cells and their microenvironment. The latest cell-derived vector, extracellular membrane microvesicles (EMVs), has been found to provide membrane protection and allowed to deliver genetic information beyond the cells. Additionally, EMV-associated microRNAs are involved in a variety of cellular pathways for tumor initiation and progression. Previous published reviews have focused on miRNA that included EMVs as a sensitive marker for tumor monitoring in clinical applications that are based on the alteration of their expression levels in conjunction with disease occurrence and progression. From the aspect of cellular crosstalk, this article will review the role of EMV-mediated microRNA transfer in tumor pathogenesis, including tumor treatment obstacles, history and features, and current research in inflammatory/immune pathologies, as well as in solid tumors and hematological malignancies. This nascent crosstalk model will provide a novel insight into complementing the classic mechanisms of intercellular communication and contribute to the potential therapeutic strategy via small RNA molecule-carrying EMVs for multimodality treatment of cancer.

Highlights

Cancer is a leading cause of death in developed nations and a growing worldwide epidemic
Extracellular membrane microvesicles, mainly aggregating and selectively including miRNAs, are uncovered as a nascent crosstalk model for cellular communication History and concept of extracellular membrane microvesicles (EMVs) Extracellular membrane microvesicles (EMVs), new performers participating in microenvironment conformation, are circular fragments of membrane released from the endosomal compartments as exosomes with diameters of 30 to 100 nm or shedding from the surface membranes of most cell types as microvesicles with diameters of 50 to 2,000 nm [10]
We describe EMVs that include both exosomes and microvesicles because they cannot be precisely separated by current methods

Summary

Introduction

Cancer is a leading cause of death in developed nations and a growing worldwide epidemic. Extracellular membrane microvesicles, mainly aggregating and selectively including miRNAs, are uncovered as a nascent crosstalk model for cellular communication History and concept of EMVs Extracellular membrane microvesicles (EMVs), new performers participating in microenvironment conformation, are circular fragments of membrane released from the endosomal compartments as exosomes with diameters of 30 to 100 nm or shedding from the surface membranes of most cell types as microvesicles with diameters of 50 to 2,000 nm [10]. This evidence opens up the possibility to manipulate tissue repair by the utilization of EMVs carrying specific miRNAs. In addition to hemodynamic disorders like nephritic ischemia, hindlimb ischemia, and myocardial ischemia, EMVs, derived from the mesenchymal cells, can protect organs from acute ischemic injury by delivering their RNA

Results

Conclusion