Dark-Side of Exosomes

Engin, Ayşe Başak

doi:10.1007/978-3-030-49844-3_4

Cited by 15 publications

(15 citation statements)

References 240 publications

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“…Furthermore, the normal cells located around the tumor cells might have absorbed some tumor-derived miRNAs 29 , and as a result, only a small amount of the tumor-derived miRNAs that existed in the stromal tissue are thus considered to ow into the blood. Some of miRNAs were also secreted from normal cells, including in ammatory cells, in response to tumor cells [30][31][32] . Thus, identifying the origin of the serum miRNAs is di cult even in the small extracellular vesicles that carry them in the blood, and no markers speci c to tumors have yet been identi ed.…”

Section: Discussionmentioning

confidence: 99%

A Validation Study for the Utility of Serum microRNA as a Diagnostic and Prognostic Marker in High-Grade Osteosarcoma Patients

Araki

Asano

Yamamoto

et al. 2022

Preprint

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In our previous study, high-grade osteosarcoma advanced locally and promoted metastasis by suppressing osteoclastogenesis via the upregulation of miR-146a-5p. Another 14 miRNAs in small extracellular vesicles were also detected 5 or more times as frequently in high-grade malignancy as in low-grade malignancy. However, the utility of these 15 miRNAs for determining the prognosis or diagnosis of osteosarcoma has not been validated in the clinical setting. We therefore aimed to assess the utility of these serum miRNAs as prognostic and diagnostic markers. Thirty osteosarcoma patients were retrospectively reviewed, excluding those with metastasis at presentation. The survival was compared according to the serum miRNA values. In addition, to confirm diagnostic competency for osteosarcoma, the serum miRNA values were compared with those in other bone tumor patients (n = 112) and healthy controls (n = 275). Osteosarcoma patients with high serum miRNA values paradoxically showed a better survival than those with low values. These patients also had higher values of serum miR-1261 than those with benign or intermediate-grade bone tumor. Serum miR-146a-5p may not be useful marker for determining the prognosis, and a larger investigation will be required to clarify its actual utility. In contrast, serum miR-1261 may be useful for differentiating benign or intermediate-grade bone tumor.

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Section: Discussionmentioning

confidence: 99%

A Validation Study for the Utility of Serum microRNA as a Diagnostic and Prognostic Marker in High-Grade Osteosarcoma Patients

Araki

Asano

Yamamoto

et al. 2022

Preprint

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Section: Evs: Another Brick In the Wallmentioning

confidence: 99%

“…Cancer-derived EVs (Ca-EVs) ability to suppress immune antitumor activity, is guaranteed by the exchange of EVs between cancerous and non-cancerous TME-residing cells, and by the secretion of immune-modulating molecules (14,21). Furthermore, the "exosome-immune suppression" and the Ca-EVs-mediated transfer of oncogenes or oncometabolites from one cell to other is also involved in the unrestrained cell proliferation and, subsequently, in the metastatic spread (14). On the other hand, Ca-EVs, may also carry tumor-associated antigens, damage associated molecular pattern (DAMPs), and immune-stimulating molecules, that can induce an immune anti-tumor response (22,23) via the recruitment and activation of immune cells in TME (24,25).…”

Section: Evs: Another Brick In the Wallmentioning

confidence: 99%

“…Inflammasome inappropriate activation, creating a proinflammatory TME and suppressing local immunity, appears as an emerging player in all the initiation to progression stages of cancer (8)(9)(10)(11). Crucial novel modulators of inflammasome are EVs that, on the basis of the different nature of their cellular source, positively or negatively affect inflammasome cascade in diverse cancerous and non-cancerous recipient cells (12)(13)(14). In this scenario, EVs, with their Janus face behavior, strongly contribute to the immune/inflammation-associated modification of TME, and play a critical role in tumorigenesis and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Vesicles and the Inflammasome: An Intricate Network Sustaining Chemoresistance

et al. 2022

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Extracellular vesicles (EVs) are membrane enclosed spherical particles devoted to intercellular communication. Cancer-derived EVs (Ca-EVs) are deeply involved in tumor microenvironment remodeling, modifying the inflammatory phenotype of cancerous and non-cancerous residing cells. Inflammation plays a pivotal role in initiation, development, and progression of many types of malignancies. The key feature of cancer-related inflammation is the production of cytokines that incessantly modify of the surrounding environment. Interleukin-1β (IL-1β) is one of the most powerful cytokines, influencing all the initiation-to-progression stages of many types of cancers and represents an emerging critical contributor to chemoresistance. IL-1β production strictly depends on the activation of inflammasome, a cytoplasmic molecular platform sensing exogenous and endogenous danger signals. It has been recently shown that Ca-EVs can activate the inflammasome cascade and IL-1β production in tumor microenvironment-residing cells. Since inflammasome dysregulation has been established as crucial regulator in inflammation-associated tumorigenesis and chemoresistance, it is conceivable that the use of inflammasome-inhibiting drugs may be employed as adjuvant chemotherapy to counteract chemoresistance. This review focuses on the role of cancer-derived EVs in tuning tumor microenvironment unveiling the intricate network between inflammasome and chemoresistance.

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“… 209 , 210 Involvement of exosomes in the development of many pathological conditions such as diabetes and its complications, Alzheimer's disease, cancer metastasis, immune suppression, and also in obesity related complications including inflammation is now recognized. 211 Lipids play an important role in the biogenesis of exosomes and particularly nSMase2, and its product ceramide has been shown to contribute to the exosome production by intraluminal vesicle budding. 212 , 213 Thus, exosomes have been shown to be enriched in ceramide and sphingomyelin compared to the parent cells.…”

Section: Nsmase2 Biochemistry and Regulationmentioning

confidence: 99%

Neutral sphingomyelinase‐2 and cardiometabolic diseases

et al. 2021

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Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feedforward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.

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Dark-Side of Exosomes

Cited by 15 publications

References 240 publications

A Validation Study for the Utility of Serum microRNA as a Diagnostic and Prognostic Marker in High-Grade Osteosarcoma Patients

A Validation Study for the Utility of Serum microRNA as a Diagnostic and Prognostic Marker in High-Grade Osteosarcoma Patients

Extracellular Vesicles and the Inflammasome: An Intricate Network Sustaining Chemoresistance

Neutral sphingomyelinase‐2 and cardiometabolic diseases

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