Tumor-Derived Apoptotic Vesicles: With Death They Do Part

Muhsin-Sharafaldine, Morad-Rémy; McLellan, Alexander D.

doi:10.3389/fimmu.2018.00957

Cited by 26 publications

(27 citation statements)

References 260 publications

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“…Unlike exosomes, microvesicles and ApoEVs bud directly from the plasma membrane, not from MVBs. The mechanism of microvesicle and ApoEV release are not well known, but ARF6 [32] and the small GTPase RHOA [33] were reported to control microvesicle shedding; caspase-3 was required for detachment of ApoEVs from the membrane [34].…”

Section: Exosomes and Other Major Types Of Extracellular Vesiclesmentioning

confidence: 99%

Exosomes in cancer development, metastasis, and immunity

Zhang

2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

645

524

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Exosomes play essential roles in intercellular communications. The exosome was discovered in 1983, when it was found that reticulocytes release 50-nm small vesicles carrying transferrin receptors into the extracellular space. Since then, our understanding of the mechanism and function of the exosome has expanded exponentially that has transformed our perspective of intercellular exchanges and the molecular mechanisms that underlie disease progression. Cancer cells generally produce more exosomes than normal cells, and exosomes derived from cancer cells have a strong capacity to modify both local and distant microenvironments. In this review, we summarize the functions of exosomes in cancer development, metastasis, and anti-tumor or protumor immunity, plus their application in cancer treatment and diagnosis/prognosis. Although the exosome field has rapidly advanced, we still do not fully understand the regulation and function of exosomes in detail and still face many challenges in their clinical application. Continued discoveries in this field will bring novel insights on intercellular communications involved in various biological functions and disease progression, thus empowering us to effectively tackle accompanying clinical challenges.

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Section: Exosomes and Other Major Types Of Extracellular Vesiclesmentioning

confidence: 99%

Exosomes in cancer development, metastasis, and immunity

Zhang

2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

645

524

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“…This in turn disrupts the membrane cytoskeleton with formation of membrane protrusions. At the same time, the Ca 2+ -dependent scramblase is activated, leading to PS exposition to the external leaflet [ 154 , 155 ].…”

Section: Microvesicle Biogenesis and Shedding—general Mechanismsmentioning

confidence: 99%

Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?

et al. 2018

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Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we focus on plasma membrane-derived microvesicles (MVs), far less appreciated than exosomes. We integrate documented mechanisms involved in MV biogenesis and shedding, focusing on the red blood cell as a model. We then provide a perspective for the relevance of plasma membrane lipid composition and biophysical properties in microvesiculation on red blood cells but also platelets, immune and nervous cells as well as tumor cells. Although only a few data are available in this respect, most of them appear to converge to the idea that modulation of plasma membrane lipid content, transversal asymmetry and lateral heterogeneity in lipid domains may play a significant role in the vesiculation process. We suggest that lipid domains may represent platforms for inclusion/exclusion of membrane lipids and proteins into MVs and that MVs could originate from distinct domains during physiological processes and disease evolution.

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“…The released protein load, comprising VEGF, FGF, IL-6, and TIMP-1, interacts with nearby cells, in turn inducing endothelial proliferation, migration, sprouting, and maturation of endothelial cell precursors and promoting angiogenesis [118,119,120,121]. In addition to shuttling oncoproteins and regulatory factors managing the metastatic process, exosomes express immune-suppressive factors (i.e., 41 kDa FasL), that inhibit T cell reaction and induce apoptosis, frequently resulting in decreased survival in cancer patients [3,33,34,35,122]. In addition, tumor-derived apoptotic vesicles, that some researchers believe to be a completely different set of exosomes, possess procoagulant activity that could increase the thrombotic state in cancer patients undergoing chemotherapy or radiotherapy [122].…”

Section: Active Role Of Cancer Exosomes In the Metastatic Cascadementioning

confidence: 99%

“…In addition to shuttling oncoproteins and regulatory factors managing the metastatic process, exosomes express immune-suppressive factors (i.e., 41 kDa FasL), that inhibit T cell reaction and induce apoptosis, frequently resulting in decreased survival in cancer patients [3,33,34,35,122]. In addition, tumor-derived apoptotic vesicles, that some researchers believe to be a completely different set of exosomes, possess procoagulant activity that could increase the thrombotic state in cancer patients undergoing chemotherapy or radiotherapy [122]. The regulatory function of exosomal proteins is also exerted through the regulatory action of EMT during the early stages of metastasis [3,58,60,70,123,124,125,126] and of mesenchymal–epithelial transition (MET) during the late stages [123,124,125,126].…”

Section: Active Role Of Cancer Exosomes In the Metastatic Cascadementioning

confidence: 99%

A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

Spugnini¹,

Logozzi

Raimo

et al. 2018

IJMS

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Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

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Tumor-Derived Apoptotic Vesicles: With Death They Do Part

Cited by 26 publications

References 260 publications

Exosomes in cancer development, metastasis, and immunity

Exosomes in cancer development, metastasis, and immunity

Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?

A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

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