The Emerging Roles of Extracellular Vesicles As Communication Vehicles within the Tumor Microenvironment and Beyond

Abstract

Tumors evolve in complex and dynamic microenvironments that they rely on for sustained growth, invasion, and metastasis. Within this space, tumor cells and non-malignant cells are in frequent communication. One specific mode of communication that has gained recent attention is the release of extracellular vesicles (EVs). EVs are lipid bilayer-bound vehicles that are released from the cell membrane and carry nucleic acids, proteins, and lipids to neighboring or distant cells. EVs have been demonstrated to influence a multitude of processes that aid in tumor progression including cellular proliferation, angiogenesis, migration, invasion, metastasis, immunoediting, and drug resistance. The ubiquitous involvement of EVs on cancer progression makes them very suitable targets for novel therapeutics. Furthermore, they are being studied as specific markers for cancer diagnostics, prognosis, and even as chemotherapy drug-delivery systems. This review focuses on the most recent advances in EV knowledge, some current and potential problems with their use, and some proposed solutions to consider for the future.

Keywords: cancer; exosome; extracellular vesicle; microvesicle; tumor microenvironment.

Figure 1

Bidirectional communication occurs between tumor cells and cells of the tumor microenvironment (TME) via exosomes and microvesicles (MVs). Exosomes and MVs carry nucleic acids, proteins, and lipids between tumor cells and cells of the TME, which influence a multitude of pathways involved in tumor progression. Exosomes are 30–100 nm in diameter and are generated within larger intracellular multivesicular bodies. They are released into the extracellular environment on fusion with the plasma membrane. MVs generally range from 100 to 1000 nm and are formed when cell components travel to the plasma membrane to be released by membrane budding.