The Role of Exosomes in Cancer Progression (original) (raw)
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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.
Exosomes: New insights into cancer mechanisms
Journal of Cellular Biochemistry, 2019
Exosomes are mobile extracellular vesicles with a diameter 40 to 150 nm. They play a critical role in several processes such as the development of cancers, intercellular signaling, drug resistance mechanisms, and cell‐to‐cell communication by fusion onto the cell membrane of recipient cells. These vesicles contain endogenous proteins and both noncoding and coding RNAs (microRNA and messenger RNAs) that can be delivered to various types of cells. Furthermore, exosomes exist in body fluids such as plasma, cerebrospinal fluid, and urine. Therefore, they could be used as a novel carrier to deliver therapeutic nucleic‐acid drugs for cancer therapy. It was recently documented that, hypoxia promotes exosomes secretion in different tumor types leading to the activation of vascular cells and angiogenesis. Cancer cell‐derived exosomes (CCEs) have been used as prognostic and diagnostic markers in many types of cancers because exosomes are stable at 4°C and −70°C. CCEs have many functional role...
Cancers, 2020
Critical processes such as growth, invasion, and metastasis of cancer cells are sustained via bidirectional cell-to-cell communication in tissue complex environments. Such communication involves the secretion of soluble factors by stromal cells and/or cancer cells within the tumor microenvironment (TME). Both stromal and cancer cells have been shown to export bilayer nanoparticles: encapsulated regulatory molecules that contribute to cell-to-cell communication. These nanoparticles are known as extracellular vesicles (EVs) being classified into exosomes, microvesicles, and apoptotic bodies. EVs carry a vast repertoire of molecules such as oncoproteins and oncopeptides, DNA fragments from parental to target cells, RNA species (mRNAs, microRNAs, and long non-coding RNA), and lipids, initiating phenotypic changes in TME. According to their specific cargo, EVs have crucial roles in several early and late processes associated with tumor development and metastasis. Emerging evidence sugges...
Exosomes and Extracellular Vesicles as Emerging Theranostic Platforms in Cancer Research
Cells, 2020
Exosomes are endosome-derived nanovesicles produced by healthy as well as diseased cells. Their proteic, lipidic and nucleic acid composition is related to the cell of origin, and by vehiculating bioactive molecules they are involved in cell-to-cell signaling, both in healthy and pathologic conditions. Being nano-sized, non-toxic, biocompatible, scarcely immunogenic, and possessing targeting ability and organotropism, exosomes have been proposed as nanocarriers for their potential application in diagnosis and therapy. Among the different techniques exploited for exosome isolation, the sequential ultracentrifugation/ultrafiltration method seems to be the gold standard; alternatively, commercially available kits for exosome selective precipitation from cell culture media are frequently employed. To load a drug or a detectable agent into exosomes, endogenous or exogenous loading approaches have been developed, while surface engineering procedures, such as click chemistry, hydrophobic i...
Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools
Cancers, 2020
Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles.
Exosomes: Definition, Role in Tumor Development and Clinical Implications
Cancer Microenvironment, 2018
Exosomes are microvesicles released by cells in both physiological and pathological situations. They are surrounded by a lipid bilayer with proteins derived from the origin cell, and contain a variety of molecules, such as nucleic acids. They represent an emerging mechanism of intercellular communication, and they play an important role in the pathogenesis of cancer, stimulating proliferation and aggressiveness of cancer cells, inducing a microenvironment favorable to tumor development and controlling immune responses. Because of the growing understanding of the potential implications of extracellular vesicles in the development of malignancies, research on exosomes, and its role as a diagnostic and therapeutic tool, constitutes nowadays a very exciting and promising field.
The role of exosomes in diagnosis of non-haematological malignancies
Chronicles of Oncology, 2018
Exosomes are nano-sized particles 'exfoliated' from a variety of cell types. They are known to facilitate exchange of messages between various cells by transporting bio-functional cargo like proteins, nucleic acids and lipids. Exosomes play a pivotal role in cellular signaling under normal physiological conditions, as well as in diseased states like cancer. They are shed in excessive amounts by cancer cells and can be harnessed from a variety of body fluids. Hence, they can serve as a convenient and less invasive biomarker for malignancies. The present work was carried out to decipher the exact status of exosomes as a liquid biopsy tool in non-haematological malignancies. Special emphasis was laid on their isolation and validation techniques. The review of literature revealed that they could serve, both as a diagnostic and prognostic marker in a variety of cancers originating from breast, naso-pharynx, colon, lung, pancreas, prostate and urinary bladder. As of now, the available body of literature on the use of exosomes as a cancer biomarker pointed towards an exciting future ahead. Indeed, exosomes have the potential to bring about a paradigm shift in the practice of personalized medicine for non-hematological malignancies.
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...
Exosomes: key players in cancer and potential therapeutic strategy
Signal Transduction and Targeted Therapy, 2020
Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.