Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes

Abstract

Since their first description, extracellular vesicles (EVs) have been the topic of avid study in a variety of physiologic contexts and are now thought to play an important role in cancer. The state of knowledge on biogenesis, molecular content and horizontal communication of diverse types of cancer EVs has expanded considerably in recent years. As a consequence, a plethora of information about EV composition and molecular function has emerged, along with the notion that cancer cells rely on these particles to invade tissues and propagate oncogenic signals at distance. The number of in vivo studies, designed to achieve a deeper understanding of the extent to which EV biology can be applied to clinically relevant settings, is rapidly growing. This review summarizes recent studies on cancer-derived EV functions, with an overview about biogenesis and molecular cargo of exosomes, microvesicles and large oncosomes. We also discuss current challenges and emerging technologies that might improve EV detection in various biological systems. Further studies on the functional role of EVs in specific steps of cancer formation and progression will expand our understanding of the diversity of paracrine signaling mechanisms in malignant growth.

Keywords: Biogenesis; Exosomes; Extracellular communication; Extracellular vesicles; Large oncosomes; Microvesicles.

Figure 1. Tumor cells release large oncosomes

Tumor sections of PC xenografts imaged by EM showing large oncosome-like features (white arrows). Size bars are 5 mm (left) and 2 mm (right).

Figure 2. Large oncosomes as new players in intercellular communication

Tumor cells communicate with various components of the tumor microenvironment by EVs. While some of the most common mechanisms of interaction between tumor-derived MV (red dots) and exosomes (green dots) with target cells have been described, those that govern the cross talk between large oncosomes and the microenvironment are still largely unknown.