Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy? (original) (raw)
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In the last few years cancer research more and more highlighted the importance of cell to cell communication in tumor progression. Among many other functional mechanisms, results evidenced the importance of miRNAs loaded into exosomes and their actions as mediators in intercellular communication, either in the tumor microenvironment or at distant sites. Deregulation of miRNA levels is a prerogative of cancer cells and is reflected in the miRNA cargo of tumor derived exosomes. Thus, learning of circulating miRNA activities add the missing piece we need to understand some unclear aspects of cancer biology. Here we summarized the current knowledge on exosome transfer capabilities between cancer cells and all the cells constituting tumor microenvironment with a particular focus on their miRNA cargos and regulatory functions. The clinical relevance of these molecular aspects is emphasized by numerous cell interactions that ultimately result in normal cell function defeat, relevant to increase tumor malignancy. The quantitative and qualitative evaluation of circulating miRNAs offers new perspective for better diagnosis and prognosis of cancer patients, eventually improving their management. 2. Exosome biogenesis and composition The term exosome (EXO) is referred to small vesicles (40−150 nm)
Journal of clinical epigenetics
Cells release into the extracellular environment, diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles. A number of studies indicate that these extracellular vehicles (EVs) mediate the interaction between cancer cells and their microenvironment; and thereby, play a critical role in the development of cancers. EVs contain cargo which consist of proteins, lipids, mRNAs, and miRNAs that can be delivered to different types of cells in nascent as well as distal locations. Discovery of this latter cargo has drawn an increasing amount of attention, due to their altering effects on the transcriptome, proteins, and subsequent cellular characteristics in recipient cells. Cancer cell derived exosomes (CCEs) have been identified in body fluids of cancer patients including urine, plasma and saliva. Because CCE content largely depends on tumor type and stage, they invariably lend great potential in serving as prognostic and diagnostic marker...
Extracellular Vesicles As miRNA Nano-Shuttles: Dual Role in Tumor Progression
Targeted oncology, 2018
Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells. Metastatic cancer cells can balance their oncogenic potential by expressing miRNAs with oncogenic function, whilst exporting miRNAs with tumor suppressor roles out of the cells. Importantly, treatment of cancer cells with specific natural and chemical compounds could induce the elimination of miRNAs with oncogenic function, thereby reducing their aggressive...
Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology
BMC clinical pathology, 2015
Both normal and diseased cells continuously shed extracellular vesicles (EVs) into extracellular space, and the EVs carry molecular signatures and effectors of both health and disease. EVs reflect dynamic changes that are occurring in cells and tissue microenvironment in health and at a different stage of a disease. EVs are capable of altering the function of the recipient cells. Trafficking and reciprocal exchange of molecular information by EVs among different organs and cell types have been shown to contribute to horizontal cellular transformation, cellular reprogramming, functional alterations, and metastasis. EV contents may include tumor suppressors, phosphoproteins, proteases, growth factors, bioactive lipids, mutant oncoproteins, oncogenic transcripts, microRNAs, and DNA sequences. Therefore, the EVs present in biofluids offer unprecedented, remote, and non-invasive access to crucial molecular information about the health status of cells, including their driver mutations, cl...
Extracellular vesicles: their role in cancer biology and epithelial-mesenchymal transition
The Biochemical journal, 2017
Cell-cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial-mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summ...
Tumor-derived extracellular vesicles: reliable tools for Cancer diagnosis and clinical applications
Cell Communication and Signaling
Background: Studies have recently revealed that almost every type of cells including tumor cells abundantly release small vesicles known as extracellular vesicles (EVs) into the extracellular milieu. EVs carry a repertoire of biological molecules including nucleic acids, proteins, lipids, and carbohydrates and transport their cargo between cells in the vicinity as well as distantly located cells and hence act as messengers of intercellular communication. In this review, we aimed to discuss the tumor-derived exosome biology and the pivotal roles of exosomes in cancer diagnosis and treatment. Methods: In the present review study, the authors studied several articles over the past two decades published on the kinetics of EVs in tumor environment as well as on the application of these vesicles in cancer diagnosis and therapy. Results: A growing body of evidence indicates that nucleic acids such as microRNAs (miRNAs) transferring by EVs participate to create a conducive tumor environment. As EV-associated miRNAs are tissue-specific and present in most biological fluids, they hold great potential for clinical application in cancer early diagnosis, prognosis, and treatment response. Furthermore, exosomes can serve as drug delivery vehicles transferring miRNAs as well as therapeutic agents to target cells. These nano-vesicles exhibit ideal properties in comparison with the synthetic carriers that attracted scientist's attention in the field of nanotechnology medicine. Scientists have employed different strategies to build exosomes-based drug delivery system. In general, two methods (direct engineering and indirect engineering) are being utilized to produce artificial exosomes. Para-clinical data have confirmed the beneficial effects of engineering exosomes in cancer therapy. Conclusion: Exosomal miRNAs hold great promise for clinical application in early diagnosis and treatment of cancers. In addition, in spite of enthusiastic results obtained by engineered exosomes, however, there is an increasing concern over the use of optimal methods for engineering exosomes and the safety of engineered exosomes in clinical trials is still unclear.
Extracellular Vesicles in Cancer
Extracellular Vesicles [Working Title]
Extracellular vesicles (EVs) represent a generic term for all the secreted vesicles, which include exosomes, microvesicles, and apoptotic bodies. EVs are key partners in the intercellular communication and play an essential role in multiple physiological and pathological conditions. EVs are shuttles for cargo molecules, such as RNA (mRNA, microRNA, and other noncoding RNAs), DNA, proteins (receptors, transcription factors, enzymes, and extracellular matrix proteins), and lipids. In pathological states, including cancer, EVs might represent either useful biomarkers or can be used for therapeutic purposes. Moreover, in cancer, it was demonstrated that EVs play an essential role in drug resistance. Here, we review the role played by EVs in the most common forms of cancer, with a special focus on ovarian and breast cancers.
Future directions of extracellular vesicle-associated miRNAs in metastasis
Annals of Translational Medicine, 2017
Numerous studies have demonstrated the dynamic cell-to-cell communication mediated by extracellular vesicles (EV) in cancer cell survival and metastasis development. EV content includes proteins, lipids, DNA, and RNA like microRNAs. Non-protein coding microRNAs play a very active role in almost all cellular processes targeting mRNAs for silencing. Different miRNA profiles have been found in different cancer types, and clarification of miRNAs packed in EV from different types of cancers will allow the understanding of metastasis and the application of miRNAs as biomolecules in diagnostic, prognostic and therapeutic approaches to fight cancer. The profound review of Dhondt et al., 2016, provides a wide view of EV miRNAs involved in various steps of the metastasis process to illustrate how the cancer cell interaction with the near and long distance microenvironment allows metastasis. These studies will surely conduce to additional patient studies to prove the relevance of EV miRNAs in metastasis in vivo. It remains to be elucidated how the tumoral cell sorts the miRNAs for secretion to send a message, and to well recognize the type of EV performing this message delivering. It will be very useful to identify whether miRNAs are delivered with post-transcriptional modifications since this is an important feature for miRNAs activity and stability.
Function of extracellular vesicle-associated miRNAs in metastasis
Cell and Tissue Research, 2016
Extracellular RNA (exRNA) is functionally transferrable from donor to recipient cells and is protected from RNAses by electrostatic interactions with proteins or by membrane encapsulation. In addition to bioactive RNA, extracellular vesicles (EVs) contain intraluminal and membraneassociated proteins. The cellular context and fitness affect the composition of EVs and thus the outcome of the communication between the EV-producer and recipient cells. Adaptive communication through EVs is particularly important between cancer cells and their local and distant environment and drives life-threatening metastatic progression. Small noncoding RNAs (miRNAs) have been reported in EV isolations and play a role in local invasion, angiogenesis, immune modulation, metastatic niche preparation, colonization and dormancy. The metastasis-related functions attributed to EVassociated miRNAs are currently increasing exponentially in the scientific literature. We must be aware that the correct and efficient separation of non-vesicular entities (soluble proteins, RNA-protein complexes and RNA-lipoprotein complexes) from EVs is necessary to determine the true contribution of EVs in any experiment that describes the molecular content or the functional consequences of the isolated material.
Oxidative Medicine and Cellular Longevity
Extracellular vesicles (EVs) are a heterogeneous group of membrane-bounded vesicles that are believed to be produced and secreted by presumably all cell types under physiological and pathological conditions, including tumors. EVs are very important vehicles in intercellular communications for both shorter and longer distances and are able to deliver a wide range of cargos including proteins, lipids, and various species of nucleic acids effectively. EVs have been emerging as a novel biotherapeutic platform to efficiently deliver therapeutic cargos to treat a broad range of diseases including cancer. This vast potential of drug delivery lies in their abilities to carry a variety of cargos and their ease in crossing the biological membranes. Similarly, their presence in a variety of body fluids makes them a potential biomarker for early diagnosis, prognostication, and surveillance of cancer. Here, we discuss the relatively least and understudied aspects of EV biology and tried to highl...