Abstract

Glioblastoma Extracellular Vesicle Specific Peptides Inhibit EV-induced Neuronal Cytotoxicity

Xiaoli Yu, Assistant Professor, University of Colorado Anschutz Medical Campus

Glioblastoma (GBM) is the most aggressive and lethal form of brain tumors. Tumor cells release extracellular vesicles (EVs) which have been shown to play a critical role in cellular communication in the tumor micro-environment. We discovered that GBM plasma EVs were smaller in size, had no relationship between size and concentration, but showed highly significant correlation between EV concentration and plasma protein concentration. Importantly, GBM EVs purified from both plasma and tumor cell line produced IgG-mediated, complement dependent cytotoxicity in neurons. We identified high affinity phage peptides for GBM EVs by screening phage-displayed random peptide libraries. Significantly, we showed that GBM EV peptides inhibit EV-induced complement-dependent cytotoxicity in neurons in dose- and time-dependent manner. Phage peptide technologies can be used for isolation and characterization of EVs derived from brain tumors. EV specific peptides can be explored for  biomarkers and mechanisms  of brain tumor EV-induced neuronal death.