Role of extracellular vesicles in glioma progression

Quezada, Claudia; Torres, Ángelo; Niechi, Ignacio; Uribe, Daniel; Contreras-Duarte, Susana; Toledo, Fernando; Martin, R. H.; Gutiérrez, Jaime; Sobrevía, Luis

doi:10.1016/j.mam.2017.12.003

Cited by 66 publications

(92 citation statements)

References 155 publications

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“…Previous studies performed in solid and hematological malignancies have already demonstrated a key role of tumor-derived MV in the progression of disease. 30,[43][44][45] In conclusion, based on i) the expression of functional adenosinergic ectoenzymes on malignant cells, ii) the upregulation of these molecules on BM-resident cells, iii) the release of immunosuppressive MV able of amplify ADO production within the BM context, as depicted in Figure 9, the results of this study may delineate a potential immune escape mechanism for metastatic NB. Further studies will evaluate whether CD38, CD39, CD203a/PC-1, and CD73 may represent novel therapeutic targets for highrisk NB patients.…”

Section: Resident Bm Cells As Well As Metastatic Nb Cells)mentioning

confidence: 63%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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Metastatic diffusion of Neuroblastoma (NB) cells in the bone marrow (BM) represents the most negative prognostic factors for NB patients. Multiple immune escape mechanisms are postulated as responsible. Our working hypothesis is that adenosine (ADO), an immunosuppressive molecule along with the ectoenzymatic pathways (CD39-CD73 and CD38-CD203a/PC-1-CD73) controlling its production, are involved in the dynamics of NB cells in the BM. The results indicate that ectonucleotidases are expressed by i) NB cell lines, ii) metastatic NB cells isolated from NB patients' BM, iii) microvesicles (MV) derived from both NB cell types and iv) resident BM cell populations. BM infiltration by NB cells increased CD203a/PC-1 and CD73 expression on lymphoid and myeloid cells, respectively. Expressions of ectoenzymes and GD2 (NB-associated marker) were higher on MV from NB patients' BM than in controls. Moreover, CD203a/PC-1 expression on BM-derived MV provide a basis for distinguishing NB patients with high or low BM infiltration. ADO production and consumption of related by-products were significantly higher when assessed on NB patients' MV than those from controls. MV isolated from NB patients' BM significantly downregulated in vitro T cell proliferation. Lastly, NB patients with worse prognosis are identified by a high percentage of CD38 + or CD73 + MV in the BM. In conclusion, ectonucleotidases are present and functional on NB cells, as well as in NB-infiltrated BM and in MV derived from BM. It is reasonable that MV are involved in BM infiltration by NB cells. Therefore, targeting these molecules may widen the therapeutic armamentarium for metastatic NB patients. ARTICLE HISTORY

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Section: Resident Bm Cells As Well As Metastatic Nb Cells)mentioning

confidence: 63%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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“…Their cargo encompasses proteins, RNA, and lipids specific for the cell of origin (3)(4)(5). In the neoplastic setting, they induce tumor progression and infiltration, sustain neoangiogenesis, inhibit immune response, and lead to chemo/radio-resistance (3,(6)(7)(8)(9)(10)(11)(12). Interestingly, extracellular vesicles can be used as circulating biomarkers because they can be easily isolated from bloodstream, urine, cerebrospinal, ascitic, amniotic, and seminal fluid (4).…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Osti

Bene

Rappa

et al. 2019

Clinical Cancer Research

209

139

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Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. Experimental Design: Plasma from healthy controls (n ¼ 33), patients with GBM (n ¼ 43), and patients with different central nervous system malignancies (n ¼ 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. Results: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. Conclusions: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

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“…Exosomes represent microscopic, membrane‐bound vesicles that are of endocytic origin and are secreted by majority of the cells in the body. Originally described as microvesicles harboring 5′‐nucleotidase activity that were secreted from neoplastic cells, exosomes were later on shown to be secreted by a wide variety of cells and display unique molecular composition. As mentioned earlier exosomes are distinguished from other EV types through their origin with MVEs/MVBs.…”

Section: The Biology Of Exosomesmentioning

confidence: 99%

Extracellular Vesicles in Glioma: From Diagnosis to Therapy

Basu

Ghosh

2019

BioEssays

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Increasing evidence indicates that extracellular vesicles (EVs) secreted from tumor cells play a key role in the overall progression of the disease state. EVs such as exosomes are secreted by a wide variety of cells and transport a varied population of proteins, lipids, DNA, and RNA species within the body. Gliomas constitute a significant proportion of all primary brain tumors and majority of brain malignancies. Glioblastoma multiforme (GBM) represents grade IV glioma and is associated with very poor prognosis despite the cumulative advances in diagnostic procedures and treatment strategies. Here, the authors describe the progress in understanding the role of EVs, especially exosomes, in overall glioma progression, and how new research is unraveling the utilities of exosomes in glioma diagnostics and development of next-generation therapeutic systems. Finally, based on an understanding of the latest scientific literature, a model for the possible working of therapeutic exosomes in glioma treatment is proposed.

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Role of extracellular vesicles in glioma progression

Cited by 66 publications

References 155 publications

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Extracellular Vesicles in Glioma: From Diagnosis to Therapy

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