Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Oct:39:82-101.
doi: 10.1016/j.mam.2013.06.004. Epub 2013 Jul 4.

Brain tumor stem cells: Molecular characteristics and their impact on therapy

David L Schonberg  1 , Daniel Lubelski  2 , Tyler E Miller  3 , Jeremy N Rich  4
Affiliations
Review

Brain tumor stem cells: Molecular characteristics and their impact on therapy

David L Schonberg et al. Mol Aspects Med. 2014 Oct.

Abstract

Glioblastoma (GBM) is the most prevalent primary brain tumor and ranks among the most lethal of human cancers with conventional therapy offering only palliation. Great strides have been made in understanding brain cancer genetics and modeling these tumors with new targeted therapies being tested, but these advances have not translated into substantially improved patient outcomes. Multiple chemotherapeutic agents, including temozolomide, the first-line treatment for glioblastoma, have been developed to kill cancer cells. However, the response to temozolomide in GBM is modest. Radiation is also moderately effective but this approach is plagued by limitations due to collateral radiation damage to healthy brain tissue and development of radioresistance. Therapeutic resistance is attributed at least in part to a cell population within the tumor that possesses stem-like characteristics and tumor propagating capabilities, referred to as cancer stem cells. Within GBM, the intratumoral heterogeneity is derived from a combination of regional genetic variance and a cellular hierarchy often regulated by distinct cancer stem cell niches, most notably perivascular and hypoxic regions. With the recent emergence as a key player in tumor biology, cancer stem cells have symbiotic relationships with the tumor microenvironment, oncogenic signaling pathways, and epigenetic modifications. The origins of cancer stem cells and their contributions to brain tumor growth and therapeutic resistance are under active investigation with novel anti-cancer stem cell therapies offering potential new hope for this lethal disease.

Keywords: Epigenetics; Glioma stem cells; Hypoxia; Microenvironment; Therapeutic resistance.

PubMed Disclaimer

Figures

Figure 1
Figure 1
GBM stem cell (GSC) microenvironment. GSCs often reside and thrive in perivascular and hypoxic niches where growth factors and cytokines promote their maintenance. In turn, GSCs up-regulate the expression, activation, and secretion of a number of niche-dependent signaling molecules and transcription factors involved in pathways such as angiogenesis, proliferation, migration, hypoxia response, etc. GSCs interact with other tumor cells and have the potential to differentiate into other cell types including endothelial cells and pericytes.
Figure 2
Figure 2
Epigenetic regulation in GSCs. Epigenetic regulation important in GSC biology includes histone methylation, DNA methylation and miRNA-mediated suppression of target gene translation. Histone methylation in GSCs is mediated by MLL1 (H3K4 methylation), Bmi1 and EZH2 (H3K27 methylation). Demethylation of these marks has been shown to be accomplished through JMJD3. Promoter DNA methylation can suppress the transcription of targets such as CD133, miRNA-211 and TAZ. MicroRNAs, such as miRNAs-124,-125b, -128, -146a, -34a, -9* and -211 regulate various aspects of GSC biology by inhibiting translation of their target genes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abdouh M, Facchino S, Chatoo W, Balasingam V, Ferreira J, Bernier G. BMI1 sustains human glioblastoma multiforme stem cell renewal. J Neurosci Off J Soc Neurosci. 2009;29:8884–8896. - PMC - PubMed
    1. Acquati S, Greco A, Licastro D, Bhagat H, Ceric D, Rossini Z, Grieve J, Shaked-Rabi M, Henriquez NV, Brandner S, Stupka E, Marino S. Epigenetic regulation of survivin by Bmi1 is cell type specific during corticogenesis and in gliomas. Stem Cells Dayt Ohio. 2013;31:190–202. - PubMed
    1. Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK, Bigner DD. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009;18:1061–1083. - PubMed
    1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–3988. - PMC - PubMed
    1. Alonso MM, Jiang H, Gomez-Manzano C, Fueyo J. Targeting brain tumor stem cells with oncolytic adenoviruses. Methods Mol Biol Clifton Nj. 2012;797:111–125. - PMC - PubMed

Publication types