Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.3 Glioma Culture Systems Introduction
cell [458]. Much of the insight into brain tumour stem cells comes directly from
NS cell research because the discovery of such stem cells in the mammalian
brain has laid the foundations for designing experiments aimed at assessing
whether the hierarchy based on stem cells seen in adult healthy brain also
exists in human brain tumours and future investigations will hopefully clarify
where the brain tumour stem cell sits along the lineage hierarchy of cells [122].
In murine models for skin carcinogenesis, the tumour phenotype arising from
overexpression of HRAS, a human gene involved in the regulation of cell divi-
sion in response to growth factor stimulation, depended on the cell compart-
ment it occurred in, with suprabasal layers yielding benign tumours and hair
follicle bulge regions, the putative location for skin stem cells, yielding inva-
sive carcinomas. Along these lines, different cells of origin might give rise to
different types of brain tumours, with the more benignant ones arising from
restricted progenitors and the more aggressive ones from stem cells or early
progenitors. The cell of origin question is hampered by limited definition of
the normal NS cell hierarchy, especially by a lack of promoters that can spec-
ify gene expression in distinct compartments of the stem cell hierarchy and
of cell surface markers that can distinguish stem cells from multipotent or
lineage-restricted progenitors. Nestin, Sox2 and CD133 identify NS cells and
progenitors but no definite lineage-restricted progenitor cells have been identi-
fied. GFAP marks a rare NS cell population as well as differentiated astrocytes,
complicating the interpretation of these studies [122].
3.3 Glioma Culture Systems
Glioma Cancer Cell Lines
The historically adopted use of cancer cell lines to delineate tumour biology
and do preclinical drug screenings needs to be re-evaluated in light of the re-
cently discovered stem cell component of solid tumours, in order to assess how
well cancer cell lines reflect this characteristic amongst others with respect
to primary tumour cultures. Phenotypic characteristics and the multitude of
genetic aberrations found within repeatedly in vitro passaged cancer cell lines
often bear little resemblance to those found within the corresponding primary
human tumour and to this end, the study by Lee et al [261] attempted to find
a more biologically relevant model system for exploring glioma biology and for
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