Epithelial-mesenchymal transition in glioblastoma progression

Abstract

Epithelial-mesenchymal transition (EMT) is a reversible biological process that occurs in epithelial cells. EMT ultimately leads to the acquisition of a mesenchymal phenotype, characterized by increased cell motility and resistance to genotoxic agents. These processes mostly overlap with the acquirement of stem cell properties in differentiated tumor cells. With regard to gliomas, the clinical picture is heterogeneous, even within the same grades and histological categories of the disease. Furthermore, the areas of invasion and responses to radiochemotherapy are markedly different among cases, and occasionally even in the same patient. Such phenotypic diversity in glioma tissues may be caused by various microenvironmental factors, as well as intrinsic genetic alterations. The current review focuses on the EMT-inducing factors that are present in gliomas; these typically vary from those observed in epithelial cancers, as no basement membrane is present. Furthermore, the most important cell-cell contact factor, E-cadherin, is rarely expressed in gliomas. The microenvironment that induces EMT in gliomas is characterized by hypoxia and the enrichment of myeloid cells following stimulation by transforming growth factor-β. Anti-vascular endothelial growth factor therapy, including the use of bevacizumab, may be a suitable candidate to modulate the glioma microenvironment.

Keywords: epithelial-mesenchymal transition; glioma; microRNA; stem cell.

Figure 1.

Scheme for the epithelial-mesenchymal transition in glioma cells. Glioma cells lose adhesion molecules and alter their cytoskeleton through a reprogramming process. It is essential that this phenotypic change is reversible, and the reverse process, termed mesenchymal-epithelial transition, is necessary for the formation of distant or disseminated tumor nodules.