Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

Abstract

Malignant glioma cells invade the surrounding brain parenchyma, by migrating along the blood vessels, thus promoting cancer growth. The biological bases of these activities are grounded in profound alterations of the metabolism and the structural organization of the cells, which consequently acquire the ability to modify the surrounding microenvironment, by altering the extracellular matrix and affecting the properties of the other cells present in the brain, such as normal glial-, endothelial- and immune-cells. Most of the effects on the surrounding environment are probably exerted through the release of a variety of extracellular vesicles (EVs), which contain many different classes of molecules, from genetic material to defined species of lipids and enzymes. EV-associated molecules can be either released into the extracellular matrix (ECM) and/or transferred to neighboring cells: as a consequence, both deep modifications of the recipient cell phenotype and digestion of ECM components are obtained, thus causing cancer propagation, as well as a general brain dysfunction. In this review, we first analyze the main intracellular and extracellular transformations required for glioma cell invasion into the brain parenchyma; then we discuss how these events may be attributed, at least in part, to EVs that, like the pawns of a dramatic chess game with cancer, open the way to the tumor cells themselves.

Identification of the potential biomarkers in patients with glioma: a weighted gene co-expression network analysis

“…Glioma is a brain tumor with a high degree of infiltration of surrounding tissue, and its ability to infiltrate normal brain tissue is a marker of poor prognosis ( 29 ). Because the brain lacks the special structure of the true lymphatic system, gliomas migrate along blood vessels and invade surrounding normal brain tissues ( 30 ). These physiological activities are based on the tumor cells expressing different programming genes, which affect the cell cycle, modify the surrounding environment, and change the extracellular matrix ( 31 ).…”

Extracellular Vesicle-Mediated Cell–Cell Communication in the Nervous System: Focus on Neurological Diseases

“…Tumor cells, derived from primary brain tumours or from metastases, use exosomes as packages to spread proteins and other molecules associated with malignancy [41,170]. Exosomes with their cargo would participate in the modulation of the tumor microenvironment, for instance by regulation of gene expression in the target cells and the functioning of the immune system, creating a pro-metastatic niche [171]. Tumor cell-derived exosomes can cross the BBB, which enhances tumor dissemination.…”

Perspectives for Ezrin and Radixin in Astrocytes: Kinases, Functions and Pathology

“…It is currently assumed that these subtypes have a common progenitor. Yet it is currently unclear if the tumour cells can alter their differentiation state depending on their environment, and if yes how they can do so [104,105,106].…”