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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Glioma Stem Cell Maintenance: The Role of the Microenvironment

Author(s): John M. Heddleston, Masahiro Hitomi, Monica Venere, William A. Flavahan, Kenneth Yang, Youngmi Kim, Sana Minhas, Jeremy N. Rich and Anita B. Hjelmeland

Volume 17, Issue 23, 2011

Page: [2386 - 2401] Pages: 16

DOI: 10.2174/138161211797249260

Price: $65

Abstract

Glioblastomas are highly lethal cancers for which conventional therapies provide only palliation. The cellular heterogeneity of glioblastomas is manifest in genetic and epigenetic variation with both stochastic and hierarchical models informing cellular phenotypes. At the apex of the hierarchy is a self-renewing, tumorigenic, cancer stem cell (CSC). The significance of CSCs is underscored by their resistance to cytotoxic therapies, invasive potential, and promotion of angiogenesis. Thus, targeting CSCs may offer therapeutic benefit and sensitize tumors to conventional treatment, demanding elucidation of CSC regulation. Attention has been paid to intrinsic cellular systems in CSCs, but recognition of extrinsic factors is evolving. Glioma stem cells (GSCs) are enriched in functional niches-prominently the perivascular space and hypoxic regions. These niches provide instructive cues to maintain GSCs and induce cellular plasticity towards a stem-like phenotype. GSC-maintaining niches may therefore offer novel therapeutic targets but also signal additional complexity with perhaps different pools of GSCs governed by different molecular mechanisms that must be targeted for tumor control.

Keywords: Glioma stem cell, cancer stem cell, microenvironment, glioma, vascular endothelial growth factor, stromal-derived factor 1, CD133, glycosylation, angiogenesis, digoxin


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