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Volume 11, Pages 1829-1841
Review Article

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

1Oncohematology Laboratory, Department of Paediatrics, University of Padova, Via Giustiniani 3, Padova 35128, Italy
2Neurosurgery, Department of Neuroscience, University of Padova, Via Giustiniani 2, Padova 35128, Italy

Received 28 July 2011; Accepted 29 September 2011

Academic Editor: Martin Gotte

Copyright © 2011 Luca Persano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called “hypoxic niche” plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing 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 preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on 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 of this model for future GBM patient management and novel therapeutic strategies development.