ABSTRACT
Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1 µm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to monitor therapy effectiveness. Whereas, small tumor-derived EVs (<1 µm) are likely to outnumber their larger counterparts, thereby offering better statistical significance, identification and quantification of small tdEVs are more challenging. In the blood of cancer patients, a subpopulation of EVs originate from tumor cells, but these EVs are outnumbered by non-EV particles and EVs from other origin. In the Dutch NWO Perspectief Cancer-ID program, we developed and evaluated detection and characterization techniques to distinguish EVs from non-EV particles and other EVs. Despite low signal amplitudes, we identified characteristics of these small tdEVs that may enable the enumeration of small tdEVs and extract relevant information. The insights obtained from Cancer-ID can help to explore the full potential of tdEVs in the clinic.
ABSTRACT
Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by 'infecting' neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan-horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS.
Subject(s)
Brain/physiology , Cell Communication/physiology , Exosomes/physiology , Models, Neurological , Nervous System Diseases/physiopathology , Biological Transport/physiology , Brain/physiopathology , Drug Delivery Systems/methods , Humans , Nervous System Diseases/drug therapyABSTRACT
The life cycle of Epstein-Barr virus (EBV) is intriguing in that the virus resides within the immune system and utilizes distinct latency expression programs to establish a persistent infection yet escaping elimination. To achieve this EBV has hijacked cellular signaling pathways to its own benefit, but deregulated viral gene expression can turn into oncogenesis. EBV like many other persistent herpes viruses has evolved ingenious tricks to evade the immune system in part by mimicking host gene function(s). Latent membrane protein 1 (LMP1) mimics CD40 signaling as part of its "normal" biological function and when deregulated, functions as a viral oncogene. LMP1 also affects cell-cell contact, cytokine and chemokine production, Ag presentation and is secreted in the extracellular milieu via immunogenic exosomes. Thus, besides its well-known growth promoting properties LMP1 modulates immune responses. Herein we discuss current knowledge regarding the role of LMP1 in immune evasion of EBV and how this strategy for establishment of persistence contributes to immune escape of EBV+ tumors.
