Intestinal epithelial cells secrete exosome–like vesicles

International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20years can explain this interest. First characterized during reticulocyte maturation, they were next characterized as a key player in the immune response and cancer immunotherapy. More recently they were characterized as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

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“…They feature a density ranging from 1.13 g/ml for B cell exosomes [2] to 1.19 g/ml for epithelial intestinal cell exosomes [6].…”

Section: A Biogenesis and Release Of Exosomes By Producer Cells: Fromentioning

confidence: 99%

“…Intestinal epithelial cells are able to secrete 2 types of exosomes originating from apical and basolateral sides and which display different proteic compositions [6].…”

Section: Page 8 Of 32mentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

476

336

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“…14,20,21 It has been shown that various types of eukaryotic cells, including hematopoietic cells and more recently tumor cells, secrete exosomelike vesicles. [5][6][7][8][9][10][11][12][13] Exosomes have diverse functions on the basis of their origins. In particular, exosomes from B lymphocytes were found to stimulate CD4ϩ T cells in vitro and exosomes from tumor-peptide-pulsed dendritic cells could activate cytolytic T cells in vivo and induce an antitumor activity.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] These extracellular vesicles are also produced by various kinds of hematopoietic cells, including mast cells, platelets, T lymphocytes, B lymphocytes and dendritic cells (DCs), as well as by intestinal epithelial cells. [5][6][7][8][9][10][11][12][13] Exosomes are known to originate from the inward budding of limiting membrane of multivesicular bodies (MVBs), and these internal vesicles of MVBs are released into the extracellular space by fusion of MVBs with the plasma membrane. 14 Proteomic analysis of DC-or B-cell-derived exosomes revealed selective enrichment of a subset of cellular proteins, including antigen-presenting proteins such as MHC class I and II molecules, heat shock proteins (HSPs), targeting-related MFG-E8 and tetraspanins such as CD9, CD63, CD81 and CD82.…”

mentioning

confidence: 99%

Exosomes: A new delivery system for tumor antigens in cancer immunotherapy

Cho

Yeo

Son

et al. 2004

Intl Journal of Cancer

140

123

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Exosomes are small membrane vesicles that are released into the extracellular environment during fusion of multivesicular bodies with plasma membrane. Exosomes are secreted by various cell types including hematopoietic cells, normal epithelial cells and even some tumor cells. They are known to carry MHC class I, various costimulatory molecules and some tetraspanins. Recent studies have shown the potential of using native exosomes as immunologic stimulants. Here, we demonstrate a novel means of using exosomes engineered to express a specific tumor antigen to generate an immune response against tumors. We expressed a target tumor antigen, human MUC1 (hMUC1), in 2 MHC typedistinct mouse cell lines, CT26 and TA3HA. Analysis of exosomes purified from these cells revealed that exosomes contained the target MUC1 antigen on their surfaces as well as other welldescribed exosomal proteins, including Hsc70 and MHC class I molecules. In addition, both autologous and allogenic exosomes were able to stimulate the activation of immune cells and suppress hMUC1-expressing tumor growth in a MUC1-specific and doserelated manner. Therefore, these data suggest that exosomes can be engineered from tumor cell lines to deliver a target immunogen capable of inducing an effective immune response and that they may represent a new cell-free tumor vaccine. © 2004 Wiley-Liss, Inc. Key words: exosomes; membrane vesicles; hMUC1; Hsc70; cell-free tumor vaccine Exosomes were initially described as small membrane vesicles (40 -90 nm in diameter), which are released from reticulocytes in order to eliminate unnecessary proteins, such as transferrin receptor (TfR) or acetylcholine esterase, during the process of their final maturation into red blood cells. [1][2][3][4] These extracellular vesicles are also produced by various kinds of hematopoietic cells, including mast cells, platelets, T lymphocytes, B lymphocytes and dendritic cells (DCs), as well as by intestinal epithelial cells. [5][6][7][8][9][10][11][12][13] Exosomes are known to originate from the inward budding of limiting membrane of multivesicular bodies (MVBs), and these internal vesicles of MVBs are released into the extracellular space by fusion of MVBs with the plasma membrane. 14 Proteomic analysis of DC-or B-cell-derived exosomes revealed selective enrichment of a subset of cellular proteins, including antigen-presenting proteins such as MHC class I and II molecules, heat shock proteins (HSPs), targeting-related MFG-E8 and tetraspanins such as CD9, CD63, CD81 and CD82. [15][16][17][18] In addition, a recent study by Hegman et al. has demonstrated that exosomes secreted by human mesothelioma cells contain a discrete set of proteins associated with antigen presentation, signal transduction, migration and adhesion. 19 The function(s) of exosomes are not well defined but have been reflected by their protein composition and cellular origins. 14,20 Although exosomes are known to discard membrane proteins such as transferrin receptors in reticulocytes, several lines of studies have sug...

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“…This could indicate that different exosome subtypes exist originating from different biogenesis pathways. Additionally, Van Niel et al showed a clear discrepancy in protein profile between EVs released from the apical or basolateral side of polarized epithelial cells [60]. Another report showed that vesicles isolated from conditioned cell medium and plasma by UC could be divided in two distinct populations by bottom-up density gradient UC.…”

Section: Ev Heterogeneitymentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

157

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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Intestinal epithelial cells secrete exosome–like vesicles

Cited by 606 publications

References 43 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes: A new delivery system for tumor antigens in cancer immunotherapy

Therapeutic and diagnostic applications of extracellular vesicles

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