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.

Tumor microenvironment complexity and therapeutic implications at a glance

“…These nanoparticles called exosomes are key to maintain homeostasis of their releasing (originating) cells [169][170][171][172]. They facilitate specific cell-cell interactions and stimulate several signaling pathways in their target cells, including cancer cells [173]. The production and release of exosomes from the tumor cells transmits a great deal of information with regards to the molecular and genetics properties, from the tumor cells to healthy ones or other abnormal cells residing nearby or at distant sites specifically designed to promote tumor invasion, metastasis and drug resistance [174].…”

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

“…Upon their infiltration into tumour lesions, these EVs participate in the elimination of non-cancer cells, such as fibroblasts and MSCs, after which they attack tumour cells. These EVs can thus exhibit direct cytotoxicity against tumour cells [49][50][51][52] (Fig. 3).…”

“…In contrast, EVs released from unaffected cancer cells reinforce the adjacent fibroblast (green) and cancer (yellow) cells, distributed over the central golden background. This effect of EVs induces cancer progression [49][50][51][52][53][54][55]. Moreover, the EVs of cancer cell origin move to the proximity of neighbouring vessels, thus inducing stimulation of angiogenesis (red of the vessel system over the pink background to the right) [46].…”

Exosomes: recruits for tumour surveillance?

“…Exosomes represent a very original way in which cells can communicate (8). These vesicles contain a large variety of molecules, not only the like of growth factors, transcription factors or hormones but also nucleic acids, most notably mRNA, miRNA and DNA [mitochondrial, single stranded, transposable elements and large (>10 kb) double strands] (9).…”