Proteome of Glioblastoma-Derived Exosomes as a Source of Biomarkers.

Stanislav Naryzhny,Luiza Garaeva,Roman Kamyshinsky,Elena Zorina,Tatiana Shtam,Arthur Kopylov,Anatoly Shlikht,Andrey Volnitskiy,Viktor Bairamukov

doi:10.3390/biomedicines8070216

Abstract

Extracellular vesicles (EV) are involved in important processes of glioblastoma multiforme (GBM), including malignancy and invasion. EV secreted by glioblastoma cells may cross the hematoencephalic barrier and carry molecular cargo derived from the tumor into the peripheral circulation. Therefore, the determination of the molecular composition of exosomes released by glioblastoma cells seems to be a promising approach for the development of non-invasive methods of the detection of the specific exosomal protein markers in the peripheral blood. The present study aimed to determine the common exosomal proteins presented in preparations from different cell lines and search potential glioblastoma biomarkers in exosomes. We have performed proteomics analysis of exosomes obtained from the conditioned culture medium of five glioblastoma cell lines. A list of 133 proteins common for all these samples was generated. Based on the data obtained, virtual two-dimensional electrophoresis (2DE) maps of proteins presented in exosomes of glioblastoma cells were constructed and the gene ontology (GO) analysis of exosome proteins was performed. A correlation between overexpressed in glial cell proteins and their presence in exosomes have been found. Thus, the existence of many potential glioblastoma biomarkers in exosomes was confirmed.

Highlights

The glioblastoma multiforme (GBM) is the most malignant form of brain tumors and one of the most aggressive types of cancer [1]
Five samples of vesicles isolated from the conditioned culture medium (CCM) of glioma cell lines were analyzed by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), and Atomic
Exosomes released by glioblastoma cells may cross the hematoencephalic barrier and carry molecular cargo into the peripheral circulation

Summary

Introduction

The glioblastoma multiforme (GBM) is the most malignant form of brain tumors and one of the most aggressive types of cancer [1]. Despite the efforts of the medical and scientific community, a reliable non-invasive method for early diagnosis of glioblastoma has not been developed up to date. Computed tomography and brain biopsy are still the main methods for the diagnosis of this disease. The need for biomarkers is becoming more apparent as the clinical management of GBM. There is a hope that EV secreted by glioblastoma cells could be a source of biomarkers detectable in the peripheral circulation [3]. EV contain an array of different types of macromolecules–proteins, nucleic acids, lipids, and metabolites–which could be considered as the candidates for biomarkers [5]

Methods

Results

Conclusion