Vesiclemia: counting on extracellular vesicles for glioblastoma patients

Sabbagh, Quentin; André-Grégoire, Gwennan; Guével, Laëtitia; Gavard, Julie

doi:10.1038/s41388-020-01420-x

Cited by 24 publications

(20 citation statements)

References 79 publications

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“…These small membrane vesicles are heterogeneous in origin, size, and quality. GBM-derived EVs are detectable in plasma and cerebrospinal fluid of GBM patients and contain a wide variety of biological materials (proteins, miRNA, mRNA, DNA, lipids, and metabolites) [ 78 ]. It has been shown that GBM- and/or GSC-derived EVs transport oncogenic information as well as pro-angiogenic cues [ 79 , 80 , 81 , 82 , 83 , 84 , 85 ].…”

Section: Sprouting Angiogenesismentioning

confidence: 99%

Tumor Vessels Fuel the Fire in Glioblastoma

Rosińska

Gavard

2021

IJMS

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Glioblastoma, a subset of aggressive brain tumors, deploy several means to increase blood vessel supply dedicated to the tumor mass. This includes typical program borrowed from embryonic development, such as vasculogenesis and sprouting angiogenesis, as well as unconventional processes, including co-option, vascular mimicry, and transdifferentiation, in which tumor cells are pro-actively engaged. However, these neo-generated vascular networks are morphologically and functionally abnormal, suggesting that the vascularization processes are rather inefficient in the tumor ecosystem. In this review, we reiterate the specificities of each neovascularization modality in glioblastoma, and, how they can be hampered mechanistically in the perspective of anti-cancer therapies.

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Section: Sprouting Angiogenesismentioning

confidence: 99%

Tumor Vessels Fuel the Fire in Glioblastoma

Rosińska

Gavard

2021

IJMS

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“…Extracellular vesicles operate as instrumental conveyors in cancer settlement and progression 44 During necroptotic cell death, MLKL phosphorylation by RIPK3 drives its oligomerization and insertion in the plasma membrane, thereby forming lytic pores 22,31,45,46 . Although several compounds were shown to trigger necroptosis in vitro in glioblastoma cell lines 47,48,49,50 , our data show that this is not the case with patient-derived GSCs most likely due to the absence of RIPK3.…”

Section: Discussionmentioning

confidence: 99%

The Necroptosis Effector MLKL drives Small Extracellular Vesicle Release and Tumour Growth in Glioblastoma

André-Grégoire

Douanne

Thys

et al. 2021

Preprint

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Extracellular vesicles (EVs) are lipid-based nano-sized particles that convey biological material from donor to recipient cells. They play key roles in tumour progression, notably in glioblastoma in which the subpopulation of Glioblastoma Stem-like Cells (GSCs) might represent a meaningful source of tumour-derived EVs. However, the mechanisms involved in the production and release of EVs by GSCs are still poorly understood. Here, we report the identification of MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of small EVs from GSCs. The targeting of MLKL by genetic, protein depletion or chemical approaches alters endosomal trafficking and EV release and reduces GSC expansion in vitro. This function ascribed to MLKL appears independent of its role during necroptosis. In vivo, pharmacological inhibition of MLKL triggers a reduction of both the tumour burden in xenografted mice and of the level of plasmatic EVs. This work reinforces the idea of a non-deadly role for MLKL in endosomal trafficking and suggests that interfering with EV biogenesis is a promising therapeutic option to sensitize glioblastoma cells to death.

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“…Numerous studies have unveiled the central role of Extracellular Vesicles (EVs) as key mediators of intercellular communication in the glioblastoma microenvironment (2)(3)(4)(5)(6)(7)(8). The term EVs is a moniker for a variety of small, heterogeneous, membrane vesicles (30-1000nm), released by virtually all cells into surrounding milieu and consecutively circulating in biofluids, such as blood, urine etc… (9).…”

Section: Introductionmentioning

confidence: 99%

“…EVs therefore act as potent mediators for cell communication in tissue and throughout fluids and body. Indeed, the EV secretory pathway is suspected to be perverted by both tumor and stromal cells, and might distribute oncogenic material and non-physiological information (2, 5, 6, 8, 10, 11). Thereby, EVs have been suggested to serve as major communication tools from and towards stem-like tumor cells, differentiated tumor cells, immune system and vascular endothelial cells, to support tumor growth, invasiveness and survival (2).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the EV secretory pathway is suspected to be perverted by both tumor and stromal cells, and might distribute oncogenic material and non-physiological information (2, 5, 6, 8, 10, 11). Thereby, EVs have been suggested to serve as major communication tools from and towards stem-like tumor cells, differentiated tumor cells, immune system and vascular endothelial cells, to support tumor growth, invasiveness and survival (2). Beside their instrumental role in transcellular message delivery, EVs quantitatively and qualitatively may vary with gender, ageing and during diseases (12, 13).…”

Section: Introductionmentioning

confidence: 99%

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The von Willebrand Factor stamps Plasmatic Extracellular Vesicles from Glioblastoma Patients

Sabbagh¹,

André-Grégoire

Nicolau

et al. 2021

Preprint

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Glioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness and resistance, as they carry and disseminate oncogenic material in the local tumor microenvironment and at distance. However, whether their quality and quantity reflect individual health status and changes in homeostasis is still not fully elucidated. Here, we separated EVs from plasma collected at different time points alongside with the clinical management of GBM patients. Our findings confirm that plasmatic EVs could be separated and characterized with standardized protocols, thereby ensuring the reliability of measuring vesiclemia, i.e. extracellular vesicle concentration in plasma. This unveils that vesiclemia is a dynamic parameter, which could be reflecting tumor burden and/or response to treatments. Further label-free liquid chromatography tandem mass spectrometry unmasks the von Willebrand Factor (VWF) as a selective protein hallmark for GBM-patient EVs. Our data thus support the notion that EVs from GBM patients showed differential protein cargos that can be further surveyed in circulating EVs, together with vesiclemia.

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Vesiclemia: counting on extracellular vesicles for glioblastoma patients

Cited by 24 publications

References 79 publications

Tumor Vessels Fuel the Fire in Glioblastoma

Tumor Vessels Fuel the Fire in Glioblastoma

The Necroptosis Effector MLKL drives Small Extracellular Vesicle Release and Tumour Growth in Glioblastoma

The von Willebrand Factor stamps Plasmatic Extracellular Vesicles from Glioblastoma Patients

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