Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.2 Brain Cancer Stem Cells Introduction
abundant in rat and human glioma cell lines and it specifies a subpopulation
of amplifying tumour cells in glioblastoma-like tumours but not in tumours
with oligodendroglioma features, making it a reliable marker to distinguish
oligodendroglioma from glioblastoma. These findings suggest that the ampli-
fying IQGAP1 + cancer cells are closer to a multipotent progenitor cell and
they represent the most aggressive cancer cell population in glioblastoma [39].
In a study by Ma et al [304], the expression of the stem cell markers CD133,
Nestin, Sox2 and Musashi-1 amongst others was investigated in 72 astrocy-
tomas of different WHO grades to find out that the expression of these markers
positively correlated with an increase in the WHO grade of the astrocytomas.
Finally, in a very interesting study by Wang et al [520], the stem-cell-like
CD133 + fraction from 14 human glioblastomas was shown to include a subset
of vascular endothelial-cadherin (CD144)-expressing cells with characteristics
of endothelial progenitors capable of maturing into endothelial cells. They
conclude that a subpopulation of cells within glioblastoma can give rise to
endothelial cells via a CD133 + /CD144 + endothelial progenitor intermediate
included in the CD133 + cancer stem-cell-like fraction. This discovery opens
up important clinical options since the strong correlation of tumour grade and
neoplastic vasculature in human gliomas indicates that agents blocking the en-
dothelial transition of tumour cells may provide a novel therapeutic strategy.
Recognition of the forebrain SVZ astrocytes as the descendants of radial glia in
the adult brain and their capacity to act as NS cells in vitro raises the prospect
that this cell type might be responsible for tumour expansion, identifying it-
self with the cancer stem cell population of the cancer stem cell hypothesis.
Therefore, although it is not yet clear whether cancer-initiating events occur
in NS cells, progenitors or differentiated cells, NS cells are attractive candi-
dates. Their self-renewal abilities would allow an oncogene to more easily
initiate uncontrolled proliferation, and their potential for transformation has
been further considered based on the observations that human brain tumours
frequently arise deep in the brain near the SVZ. In p53 -/- mice, more prolifer-
ative activity is found in the SVZ and more neurospheres can be isolated from
this region, suggesting an expansion of the NS cell pool, which may make the
area more susceptible to neoplastic transformation [122]. Moreover, normal NS
cells were found in the CD133 + population of the normal human fetal brain,
again suggesting that the cell of origin of brain tumours may be a normal NS
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