MicroRNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer

Abstract

Cancer-cell communication is an important and complex process, achieved through a diversity of mechanisms that allows tumor cells to mold and influence their environment. In recent years, evidence has accumulated indicating that cells communicate via the release and delivery of microRNAs (miRNAs) packed into tumor-released (TR) exosomes. Understanding the role and mode of action of miRNAs from TR exosomes is of paramount importance in the field of cancer biomarker discovery and for the development of new biomedical applications for cancer therapeutics. In this review, we focus on miRNAs secreted via TR exosomes, which by acting in a paracrine or endocrine manner, facilitate a diversity of signaling mechanisms between cancer cells. We address their contribution as signaling molecules, to the establishment, maintenance, and enhancement of the tumor microenvironment and the metastatic niche in cancer. Finally, we address the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and their impact as a biomedical tool in cancer therapeutics.

miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients

“…EV mediated miRNA transfer has been proposed as a mechanism of inter cellular communication [46]. However, the stoichiometry of miRNA per EV (< 1 molecule per 150-85,000 EVs) and the number of miRNAs required for modulating intercellular physiology (>100) [47] suggest that efficient and selective cellular uptake of EV enriched in miRNA would be required for EV-mediated miRNA transfer to be biologically plausible.…”

Stem cell-derived exosomes: a novel vector for tissue repair and diabetic therapy

“…Exosomes facilitate intercellular communication by acting as vectors for paracrine signaling (Tetta et al 2013, Salido-Guadarrama et al 2014. Exosomes are believed to be involved in cross-talk between glial cells and neurons, facilitating axon myelination, repair of neurological damage and other essential functions (Krämer-Albers & White 2011, Lopez-Verrilli & Court 2012, Sharma et al 2013.…”

“…Exosomes circulating in the blood and lymph are believed to play a significant role in antigen presentation via ingestion by antigen-presenting cells (Raposo et al 1996, Théry et al 2009, Alexander et al 2015. There is also evidence that circulating exosomes may play a role in cancer development (Salido-Guadarrama et al 2014). However, while circulating EVs, including exosomes, are plentiful, they have been found in multiple studies to possess very short half-lives of 2-5 min in the blood.…”

Pathological Effects of Exosomes in Mediating Diabetic Cardiomyopathy

“…Also, fatty acids can affect miRNA expression levels; for example, miRNA-34a and miRNA-146 expression levels were up-regulated by increased levels of fatty acids concentrations [153, 154]. Functionally, biologic effects of exosomes can be local or remote by delivering coded messages from the cell of origin to recipient cell via releasing them into inter-cellular fluid or blood circulation [155]. …”