Exosome-Based Cell-Cell Communication in the Tumor Microenvironment.
TL;DR: The role of exosomes in the communication between tumor and tumor-associated cells is highlighted, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.
Abstract: Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased), ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.
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TL;DR: Altered of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained, and miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.
Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.
804 citations
TL;DR: The history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges are discussed.
Abstract: Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.
613 citations
TL;DR: The current state-of-the-art of using exosomes or exosome-inspired systems for drug delivery is provided and the various approaches investigated and the shortcomings of each approach are reviewed.
Abstract: The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here, we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges which have been identified to date in this field are summarized.
366 citations
Cites background from "Exosome-Based Cell-Cell Communicati..."
...The most recent discoveries in the field of extracellular vesicles are unravelling exciting concepts on intercellular communication pathways [1, 2]....
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27 Mar 2019
TL;DR: The current knowledge in exosome biogenesis, their roles in disease progression, and therapeutic applications and opportunities in bioengineering are summarized and the established and emerging technological developments inExosome isolation and characterization are highlighted.
Abstract: Exosomes are small (∼30–140 nm) lipid bilayer-enclosed particles of endosomal origin. They are a subset of extracellular vesicles (EVs) that are secreted by most cell types. There has been growing interest in exosome research in the last decade due to their emerging role as intercellular messengers and their potential in disease diagnosis. Indeed, exosomes contain proteins, lipids, and RNAs that are specific to their cell origin and could deliver cargo to both nearby and distant cells. As a result, investigation of exosome cargo contents could offer opportunities for disease detection and treatment. Moreover, exosomes have been explored as natural drug delivery vehicles since they can travel safely in extracellular fluids and deliver cargo to destined cells with high specificity and efficiency. Despite significant efforts made in this relatively new field of research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. In this review, we summarize the current knowledge in exosome biogenesis, their roles in disease progression, and therapeutic applications and opportunities in bioengineering. Furthermore, we highlight the established and emerging technological developments in exosome isolation and characterization. We aim to consider critical challenges in exosome research and provide directions for future studies.
281 citations
TL;DR: The characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer are summarized and a deeper understanding of the role ofExosomes in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.
Abstract: Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.
250 citations
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...Various mechanisms have been proposed [52]....
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References
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
"Exosome-Based Cell-Cell Communicati..." refers background in this paper
...…in the immune editing of the primary tumor niche, but also in the pre-metastatic and metastatic niches, as they can outsmart stromal and immune players into overcoming the immune response (Hanahan and Weinberg, 2011), fostering the setup of pro-metastatic microenvironments (Syn et al., 2016)....
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...One of the hallmarks of cancer is the ability of tumor cells to employ different strategies to evade the host immune surveillance (Hanahan and Weinberg, 2011)....
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TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
8,664 citations
"Exosome-Based Cell-Cell Communicati..." refers background in this paper
...In fact, tumor-derived exosomes have been shown to hijack the immune surveillance program of the host by amplifying tumor-derived signals, including those involved in inflammation, and in certain cases, tumorigenesis (Grivennikov et al., 2010; Cavallo et al., 2011) and escape of...
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...…immune surveillance program of the host by amplifying tumor-derived signals, including those involved in inflammation, and in certain cases, tumorigenesis (Grivennikov et al., 2010; Cavallo et al., 2011) and escape of tumor cells from the immune system (Wieckowski et al., 2009; Whiteside, 2013)....
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TL;DR: Recent evidence suggests that differential modulation of the chemokine system integrates polarized macrophages in pathways of resistance to, or promotion of, microbial pathogens and tumors, or immunoregulation, tissue repair and remodeling.
5,568 citations
"Exosome-Based Cell-Cell Communicati..." refers background in this paper
...…macrophages can be educated into Tumor-Associated Macrophages (TAMs) displaying M2 characteristics, promoting angiogenesis and releasing pro-tumorigenic growth factors, chemokines and cytokines (Mantovani et al., 2004; Rogers and Holen, 2011; Quatromoni and Eruslanov, 2012; Schiavoni et al., 2013)....
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TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Abstract: Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.
4,118 citations
TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
3,836 citations
"Exosome-Based Cell-Cell Communicati..." refers background in this paper
...One of the factors involved in the activation of these cells, frequently named Cancer-Associated Fibroblasts (CAFs), is Transforming Growth Factor beta (TGF-β) (Tomasek et al., 2002), which can be carried to the extracellular milieu by exosomes and induce differentiation of CAFs (Webber et al....
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...…factors involved in the activation of these cells, frequently named Cancer-Associated Fibroblasts (CAFs), is Transforming Growth Factor beta (TGF-β) (Tomasek et al., 2002), which can be carried to the extracellular milieu by exosomes and induce differentiation of CAFs (Webber et al., 2010, 2015)....
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