Exosomes: From biogenesis and secretion to biological function

German Cancer Research Center (DKFZ), Tumor Immunology Program, D010/TP3, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Immunology Letters (Impact Factor: 2.51). 12/2006; 107(2):102-8. DOI: 10.1016/j.imlet.2006.09.005
Source: PubMed


Exosomes are small microvesicles that are released from late endosomal compartments of cultured cells. Recent work has shown that exosome-like vesicles are also found in many body fluids such as blood, urine, ascites and amnionic fluid. Although the biological function of exosomes is far from being fully understood, exosomes may have general importance in cell biology and immunology. The present review aims to address some of the facets of exosome research with particular emphasis on the immunologist's perspective: (i) exosomes as a novel platform for the ectodomain shedding of membrane proteins by ADAMs and (ii) recent findings on the role of exosomes in tumor biology and immune regulation.

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Available from: Michael P Sanderson, Aug 19, 2014

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Article: Exosomes: From biogenesis and secretion to biological function

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    • "In addition, the complicated milieu of extracellular signals is increased by the sheer number of cells generating exosomes which reside in the TME. B-and T-lymphocytes, dendritic cells, neurons, intestinal epithelial cells, and tumor cells all release exosomes (Denzer et al., 2000; Keller et al., 2006; Simpson et al., 2009). In particular, it has been shown that human tumor cells release TEX constitutively (Wolfers et al., 2001). "
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    ABSTRACT: The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by tumor cells themselves contribute in creating an environment mostly favorable but sometimes detrimental to the tumor. Survivin, one of the key members of the inhibitor of apoptosis (IAP) family of proteins, has been shown in the cytoplasm, mitochondria, nucleus, and most recently in the extracellular space, transported via small membrane bound vesicles called exosomes. Exosomes are secreted from hematopoietic, non-hematopoietic, tumor, and non-tumor cells, shuttling essential molecules such as proteins, RNAs, and microRNAs, all believed to be important for cell-cell and cell-extracellular communication. In this review, we discuss exosomal Survivin and its role in modifying the tumor microenvironment.
    Histology and histopathology 06/2015; 30(1):43-50. · 2.10 Impact Factor
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    • "The term EV includes different secreted membrane-enclosed vesicles such as exosomes and microvesicles, however there are no specific markers that distinguish subsets of EV from one the other [4]. Most cell types, including cardiomyocytes, actively secrete EV through exocytosis by fusion of multi-vesicular bodies with the plasma membrane or through budding from the cell membrane [5] [6] [7]. "
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    ABSTRACT: Background: Extracellular vesicles (EVs) are thought to exert protective effects after ischemic and remote ischemic preconditioning. It is not well understood which EV content factors are most relevant for protective effects. We hypothesize that ischemic preconditioning leads to qualitative changes in EV mRNA content and quantitative changes in EV size and number. Methods: Using an in vivo porcine ischemic preconditioning model, EVs were collected from coronary venous blood, and isolated by differential ultracentrifugations. The presence and purity of EV were verified by electron microscopy and Western blot, and EV number was assessed by nanoparticle tracking analysis. The mRNA EV was identified by microarray. Results: Gene ontology analysis showed enrichment of EV mRNA coding for proteins associated with regulation of transcription, translation, extracellular matrix, morphogenic development and feeding behavior. There were 11,678 different mRNA transcripts detected in EV, where a total of 1103 was significantly increased or decreased after preconditioning, of which 638 mRNA sequences were up-regulated and/or emerged due to preconditioning. Several of them have known association with ischemic preconditioning. There was no significant difference in EV quantity or size before and after preconditioning. Conclusions: These findings demonstrate in an in vivo model that myocardial ischemic preconditioning influences the composition of mRNA in EV, including gene transcripts for proteins associated with the protective effect of ischemic preconditioning. The finding that preconditioned parental cells release EV containing mRNA that is qualitatively different from those released by non-preconditioned cells shows the importance of the external milieu on parental cell EV production.
    05/2015; 21. DOI:10.1016/j.ijcha.2015.05.006
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    • "Upon binding, exosomes can enter target cells in one of two ways: by being taken up by the target cell's endocytic pathway or by fusing to the target cell's membrane and releasing its contents directly into the cytoplasm. Exosomes are increasingly recognized as mediators of intercellular communication due to their capacity to merge with and transfer a repertoire of bioactive molecular content (cargo) to recipient cells [24] [25]. "
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    ABSTRACT: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n=248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ontoexpress). Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin - an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis. Copyright © 2015. Production and hosting by Elsevier B.V.
    Journal of the Egyptian National Cancer Institute 02/2015; 101(2). DOI:10.1016/j.jnci.2015.02.002
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