The von Willebrand factor stamps plasmatic extracellular vesicles from glioblastoma patients

Abstract

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.

Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma

“…To control whether this beneficial action was accompanied by a change in EV release from the tumor grafts, murine blood was collected at sacrifice, mouse host and human donor circulating EVs were isolated and the abundance of EVs from human tumor cell origin was estimated with human CD63 ELISA ( Figure 6 K). In keeping with the idea that vesiclemia, i.e., the concentration of EVs in plasma ( Sabbagh et al., 2020 ), correlated with tumor evolution ( Osti et al., 2019 ; Sabbagh et al., 2021 ), the abundance of human origin EVs was dampened in animals that received human-targeting pharmacological compound NSA ( Figure 6 K). Mirroring the in vitro situation, the level of M6PR was superior in the EV fractions from NSA-challenged mice peripheral blood, as compared to plasmatic EVs from vehicle-receiving animals ( Figure 6 K).…”

“…Furthermore, monitoring the level of circulating EVs in the bloodstream might reflect tumor size. Indeed, GBM patients have increased vesiclemia ( André-Grégoire et al., 2018 ; Sabbagh et al., 2021 ), while resection normalized these values ( Osti et al., 2019 ). Thus, the level of plasmatic EVs may assist in the clinical management of GBM patients, and/or anticipate recurrence as a companion diagnostic tool.…”

Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review

“…Each particle is tracked and processed individually. ILM has recently been installed into a commercially available instrument Videodrop (Myriade, Paris, France) and was hitherto used to analyze microorganisms in marine water [ 115 ], viruses [ 116 ] and extracellular vesicles [ 47 , 117 ]. ILM enables non-invasive assessment of number density and R h of particles smaller than 500 nm, and therefore, assessment of diluted plasma samples directly without performing isolation that may considerably transform the constituents.…”

Mesenchymal stem/stromal cells in the pathogenesis and regenerative therapy of inflammatory bowel diseases

“…Extracellular vesicles (EVs), including exosomes, are nanoscale microvesicles released by cells that play an important role in intercellular communication via transferring cargos containing various bioactive components (protein, DNA, mRNA, and non-coding RNA) involved in various of physiological and pathological processes ( 73 , 74 ). There is increasing evidence that MSC-derived EVs display powerful therapeutic effects in several preclinical models of inflammatory diseases, suggesting that MSC-EVs may be a promising cell-free therapy because their properties are relatively stable and the safety risk is lower than that of the cell-producing similar products ( 75 , 76 ).…”