Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins

Subra, Caroline; Grand, David; Laulagnier, Karine; Stella, Alexandre; Lambeau, Gérard; Paillasse, Michaël R.; Médina, Philippe de; Monsarrat, Bernard; Fougère, Bertrand; Silvente-Poirot, Sandrine; Poirot, Marc; Record, Michel

doi:10.1194/jlr.m003657

Cited by 533 publications

(468 citation statements)

References 79 publications

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“…Similar conclusion can be drawn from observations performed in the mast cell line RBL-2H3 [9]. This type of cell contains about 30 MVBs [9] (a) , which means that one RBL-2H3 cell could contain 3000 ILVs, providing that all MVBs were filled. Actually ILV release is sectorized in the cell, i.e is limited in some region of the cell periphery, indicating that the whole MVB cell content is not released at once.…”

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

confidence: 82%

“…Subsequently, the repartition of proteins between the two leaflets of the plasma membrane should be maintained in the ILVs, which progressively accumulate during endosome maturation. However phospholipid asymmetry may be not preserved during ILV formation since exosomes appear to have a similar lipid composition between the two membrane leaflet [8], consistent with the presence of a phospholipid scramblase [9].Thus, late endosomes can accumulate up to hundred intraluminal vesicles (ILVs) [10]. Similar conclusion can be drawn from observations performed in the mast cell line RBL-2H3 [9].…”

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

confidence: 57%

“…However phospholipid asymmetry may be not preserved during ILV formation since exosomes appear to have a similar lipid composition between the two membrane leaflet [8], consistent with the presence of a phospholipid scramblase [9].Thus, late endosomes can accumulate up to hundred intraluminal vesicles (ILVs) [10]. Similar conclusion can be drawn from observations performed in the mast cell line RBL-2H3 [9]. This type of cell contains about 30 MVBs [9] (a) , which means that one RBL-2H3 cell could contain 3000 ILVs, providing that all MVBs were filled.…”

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

confidence: 99%

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Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

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462

336

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

confidence: 82%

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

confidence: 57%

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

confidence: 99%

See 1 more Smart Citation

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

Self Cite

462

336

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show abstract

“…These interactions, possibly preceded by surfing onto filopodia according to recent observations [140], mostly lead to cell uptake via one of the common endocytosis pathways (i.e. clathrin-and caveolin-dependent endocytosis, lipid raft-mediated endocytosis, macropinocytosis or phagocytosis) [105,139]. It is also interesting to note that inhibition of a given pathway is almost never able to completely abrogate the EV uptake, hinting toward the involvement of multiple uptake mechanisms and/or reflecting EV heterogeneity [139].…”

Section: Intracellular Trafficking Of Evsmentioning

confidence: 97%

“…Moreover, many reports focus on a specific component of EVs, e.g. small non-coding RNA such as miRNAs, often neglecting the true complexity of the EV composition in which lipids and proteins likely also play a key role [105]. As a result of this complexity, EVs can simultaneously interfere with different signaling pathways, leading to pleiotropic effects.…”

Section: Harnessing the Intrinsic Biological Effect Of Evsmentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

153

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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Metabolomic profile of cancer stem cell‐derived exosomes from patients with malignant melanoma

et al. 2020

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Malignant melanoma (MM) is the most aggressive and life-threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient-derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem-like properties. Exosomes derived from CSCs and serums from patients with MM were characterized and their metabolomic profile was analyzed by high-resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared to those from differentiated tumour cells, and also in serumderived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC-derived exosomes and those derived from patients with MM such as the glycerophosphocoline PC 16:0/0:0. To our knowledge, this is the first metabolomics-based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC-derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.

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Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins

Cited by 533 publications

References 79 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Therapeutic and diagnostic applications of extracellular vesicles

Metabolomic profile of cancer stem cell‐derived exosomes from patients with malignant melanoma

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