A Comprehensive Picture of Extracellular Vesicles and Their Contents. Molecular Transfer to Cancer Cells (original) (raw)
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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...
Frontiers in immunology, 2018
Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptot...
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.
Extracellular Vesicles – Biomarkers and Effectors of the Cellular Interactome in Cancer
Frontiers in Pharmacology, 2013
In multicellular organisms both health and disease are defined by patterns of communication between the constituent cells. In addition to networks of soluble mediators, cells are also programed to exchange complex messages pre-assembled as multimolecular cargo of membraneous structures known extracellular vesicles (EV). Several biogenetic pathways produce EVs with different properties, and known as exosomes, ectosomes, and apoptotic bodies. In cancer, EVs carry molecular signatures and effectors of the disease, such as mutant oncoproteins, oncogenic transcripts, microRNA, and DNA sequences. Intercellular trafficking of such EVs (oncosomes) may contribute to horizontal cellular transformation, phenotypic reprograming, and functional re-education of recipient cells, both locally and systemically. The EV-mediated, reciprocal molecular exchange also includes tumor suppressors, phosphoproteins, proteases, growth factors, and bioactive lipids, all of which participate in the functional integration of multiple cells and their collective involvement in tumor angiogenesis, inflammation, immunity, coagulopathy, mobilization of bone marrowderived effectors, metastasis, drug resistance, or cellular stemness. In cases where the EV role is rate limiting their production and uptake may represent and unexplored anticancer therapy target. Moreover, oncosomes circulating in biofluids of cancer patients offer an unprecedented, remote, and non-invasive access to crucial molecular information about cancer cells, including their driver mutations, classifiers, molecular subtypes, therapeutic targets, and biomarkers of drug resistance. New nanotechnologies are being developed to exploit this unique biomarker platform. Indeed, embracing the notion that human cancers are defined not only by processes occurring within cancer cells, but also between them, and amidst the altered tumor and systemic microenvironment may open new diagnostic and therapeutic opportunities.
Reshaping the tumor microenvironment: extracellular vesicles as messengers of cancer cells
Carcinogenesis, 2020
The tumor microenvironment (TME) comprises an assortment of immune and non-immune cells. The interactions between the cancer cells and their surrounding TME are known to be a cardinal factor in all stages of cancer progression, from initiation to metastasis. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are considered two of the most abundant TME members associated with poor prognosis in various cancer types. Intercellular communication between the cancer cells and TME cells might occur via direct cell–cell contact or achieved through secreted factors such as cytokines, growth factors and extracellular vesicles (EVs). EVs are released by almost every cell type and by cancer cells in particular. EVs are loaded with unique molecular cargos that might include DNA, proteins, RNA and lipids, commonly reflecting the physiological traits of their donor cells. Once released, EVs are capable of initiating short- and long-distance communication in an autocrine, ...
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...
Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2018
Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meetin...
Extracellular vesicles: Unraveling their physiology and role in cancer
Journal of entomology and zoology studies, 2018
Extracellular vesicles (EVs) have been thoroughly studied from different physiological contexts and now there are strong evidences that they play an important role in cancer. They have a bimodal role in cancer wherein they can manipulate the local and systemic environment to aid in cancer growth and dissemination as well as program the immune system to elicit an anti-tumor response. The amount of information on their formation, nature of cargo contained within them and horizontal communication of different types of cancer EVs has expanded considerably in recent years. Herein, we discuss biogenesis, physiological functions and contents of exosomes as well as their contribution to tumorigenesis.
Signaling by Extracellular Vesicles Advances Cancer Hallmarks
Mammalian cells secrete various extracellular vesicles (EVs; exosomes, micro-vesicles, and apoptotic bodies) that differ in biogenesis, composition, and function. Each vesicle type can originate from normal or cancerous cells, transfer molecular cargo to both neighboring and distant cells, and modulate cellular behaviors involved in eubiology and pathology, such as tumor development. Here, we review evidence for the role of EVs in the establishment and maintenance of cancer hallmarks, including sustaining proliferative signaling, evading growth suppression, resisting cell death, reprogramming energy metabolism, acquiring genomic instability, and remodeling the tumor microen-vironment. We also discuss how EVs are implicated in the induction of angio-genesis, control of cellular invasion, initiation of premetastatic niches, maintenance of inflammation, and evasion of immune surveillance. The deeper understanding of the biology of EVs and their contribution to the development and progression of tumors is leading to new opportunities in the diagnosis and treatment of cancer.
Frontiers in Cell and Developmental Biology, 2021
Cancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatme...