Extracellular vesicles in cancer — implications for future improvements in cancer care

Abstract

The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell–cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell–cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics.Emerging evidence indicates that tumour-derived extracellular vesicles (EVs), notably exosomes, mediate intercellular communication to promote cancer development and progression. Herein, the authors discuss EV properties and physiological functions, particularly their pro-metastatic effects, and highlight the diagnostic and therapeutic potential of EVs in cancer.Key pointsExosomes and shed microvesicles are two classes of small lipid-encapsulated extracellular vesicles (EVs) that transmit molecular messengers (functional proteins and nucleic acids) between cells to alter the phenotype of recipient cells.Each class of EVs has a distinct mechanism of biogenesis, and within each class, subtypes (subpopulations) exist that can be distinguished by their distinct protein and RNA signatures.The participation of exosomes in signalling between tumour cells and the microenvironment aids the establishment of the pre-metastatic niche and facilitates tumour progression.Circulating exosomes containing tumour-specific molecular signatures (oncoproteins, mRNAs, long non-coding RNAs, and DNA fragments) have clinical utility as next-generation biomarkers for liquid biopsy in cancer diagnosis and management.Standardized isolation protocols for EV subpopulations are required to enable interlaboratory data comparison and for the advancement of their clinical utility.Exosomes have potential as vehicles for the delivery of therapeutic agents and also as anticancer vaccines and could possibly guide changes in clinical practice.