The Three-Layer Concentric Model of Glioblastoma: Cancer Stem Cells, Microenvironmental Regulation, and Therapeutic Implications

Abstract EN

Tumors arising in the central nervous system are thought tooriginate from a sub-population of cells named cancer stem cells(CSCs) or tumor initiating cells (TICs) that possess an immaturephenotype, combined with self-renewal and chemotherapy resistancecapacity.

Moreover, in the last years, these cells have beenidentified in particular brain tumor niches fundamental forsupporting their characteristics.

In this paper, we report studiesfrom many authors demonstrating that hypoxia or the so called“hypoxic niche” plays a crucial role in controlling CSC molecularand phenotypic profile.

We recently investigated the relationshipexisting between Glioblastoma (GBM) stem cells and their niche,defining the theory of three-concentric layers model for GBM mass.

According to this model, GBM stem cells reside preferentiallywithin the hypoxic core of the tumour mass, while moredifferentiated cells are mainly localized along the peripheral andvascularized part of the tumour.

This GBM model providesexplanation of the effects mediated by the tumour microenvironmenton the phenotypic and molecular regulation of GBM stem cells,describing their spatial distribution in the tumor bulk.

Moreover,we discuss the possible clinical implications of the creation ofthis model for future GBM patient management and novel therapeuticstrategies development.