Brain Tumor-Derived Extracellular Vesicles as Carriers of Disease Markers: Molecular Chaperones and MicroRNAs

Abstract

Primary and metastatic brain tumors are usually serious conditions with poor prognosis, which reveal the urgent need of developing rapid diagnostic tools and efficacious treatments. To achieve these objectives, progress must be made in the understanding of brain tumor biology, for example, how they resist natural defenses and therapeutic intervention. One resistance mechanism involves extracellular vesicles that are released by tumors to meet target cells nearby or distant via circulation and reprogram them by introducing their cargo. This consists of different molecules among which are microRNAs (miRNAs) and molecular chaperones, the focus of this article. miRNAs modify target cells in the immune system to avoid antitumor reaction and chaperones are key survival molecules for the tumor cell. Extracellular vesicles cargo reflects the composition and metabolism of the original tumor cell; therefore, it is a source of markers, including the miRNAs and chaperones discussed in this article, with potential diagnostic and prognostic value. This and their relatively easy availability by minimally invasive procedures (e.g., drawing venous blood) illustrate the potential of extracellular vesicles as useful materials to manage brain tumor patients. Furthermore, understanding extracellular vesicles circulation and interaction with target cells will provide the basis for using this vesicle for delivering therapeutic compounds to selected tumor cells.

Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model

“…The GBM microenvironment is a complex, dynamic, and interactive system. GBM cells and various components of the TME influence each other directly through cell-cell contact or indirectly through the release of soluble factors, such as cytokines, chemokines, growth factors, and extracellular matrix (ECM) remodeling enzymes, as well as via extracellular vesicles (EVs) [21][22][23][24][25][26]. In addition to these communication mechanisms, GBM cells use nanotubes, gap junctions, free DNA, horizontal DNA transfer, and circulating tumor cells to interact with other tumor and non-tumor cells.…”

Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

“…Other EV components, such as mRNA and miRNA, also have the potential as tumor diagnostic markers. miRNAs can be exchanged between cells via exosomes and their detection and analysis provides information about the parental cell [143,223,[235][236][237]. The diversity of transcriptomic profiles observed in glioma cells is mirrored in EVs derived from these cells.…”

The Microbiota Is Not an Organ: Introducing the Muco-Microbiotic Layer as a Novel Morphofunctional Structure

“…Therefore, investigation of EVs is useful to highlight mechanisms that may determine health or disease. Furthermore, as EVs carry genetic material and proteins that may affect different signaling pathways in the target cells and organs, and since they are commonly found in biological fluids and tissue, they can be used as noninvasive and easily accessible disease biomarkers [48][49][50][51][52][53]. As stated above, in different diseases, cells can produce EVs with alterations in number and molecular content compared to physiological conditions, and accumulating evidence demonstrates their role in cancer, in which the application of EVs may be helpful for early diagnostics and the identification of new therapeutic targets [52].…”