Open AccessGlioma Stem Cell Maintenance: The Role of the Microenvironment
Author(s) -
John M. Heddleston,
Masahiro Hitomi,
Monica Venere,
William Flavahan,
Kunlong Yang,
Youngmi Kim,
Sana Minhas,
Jeremy Rich,
Anita B. Hjelmeland
Publication year - 2011
Publication title -
current pharmaceutical design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 159
eISSN - 1873-4286
pISSN - 1381-6128
DOI - 10.2174/138161211797249260
Subject(s) - cancer stem cell , stem cell , biology , glioma , angiogenesis , cancer research , epigenetics , stromal cell , phenotype , tumor microenvironment , microbiology and biotechnology , genetics , gene , tumor cells
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.