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2011;17 (23): 2386-401.

Glioma stem cell maintenance: the role of the microenvironment.

John M Heddleston, Masahiro Hitomi, Monica Venere, William A Flavahan, Kenneth Yang, Youngmi Kim, Sana Minhas, Jeremy N Rich, Anita B Hjelmeland
Author Information
  1. John M Heddleston: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
PMID: 21827414 DOI: 10.2174/138161211797249260

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.

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Grants

  1. R01 CA129958/NCI NIH HHS
  2. R01 CA151522/NCI NIH HHS
  3. R01 CA154130/NCI NIH HHS
  4. T32 GM007250/NIGMS NIH HHS

MeSH Term

Angiogenesis Inhibitors
Animals
Antibodies, Monoclonal, Humanized
Bevacizumab
Biomarkers, Tumor
Brain Neoplasms
Cell Hypoxia
Cellular Microenvironment
Epigenesis, Genetic
Glioblastoma
Humans
Neoplastic Stem Cells
Oxygen
Pluripotent Stem Cells
Vascular Endothelial Growth Factor A

Chemicals

Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Biomarkers, Tumor
Vascular Endothelial Growth Factor A
Bevacizumab
Oxygen
Journal Article Review
Article has an altmetric score of 1

Word Cloud

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