Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.2 Brain Cancer Stem Cells Introduction
tion factor and become cancer stem cells [457]. This paradox may be resolved
if the non-cancer stem cells in a precursor cell population could also serve as
targets of mutation, leading to clonal succession and, therefore, tumour pro-
gression [182]. For example, when tumour spheres derived from highly vascular
glioblastomas were transplanted into mice, the initial tumours demonstrated
low-grade glioma phenotype without any sign of angiogenesis. However, upon
serial transplantation in vivo, the tumour cells developed a highly malignant
phenotype with extensive angiogenesis and necrosis being present in the tu-
mours. This finding highlights a well-established fact that tumour cells evolve
and if more malignant and less differentiated cancer cells have growth advan-
tage, they will be selected for and expanded in the tumour. Therefore, as
tumours progress, the line between cancer stem cells and the rest of tumour
cells might gradually become blurred and can even disappear [457].
Finally, the recent finding that, depending on the tumour analysed, glioblas-
toma cancer stem cells can be CD133 + or CD133 - cells, also emphasises that
either we do not have good markers for cancer stem cells or all tumour cells
are tumourigenic at varying degree, which brings us back to what we already
know about tumours being diverse, genetically unstable, and evolving due to
the intratumoural diversity of cellular genotypes and phenotypes. Especially
in light of the recent finding that normal human differentiated cells can be
converted into functional pluripotent embryonic stem cells by expressing the
right combination of transcription factors [215,226,462], it is a possibility that
more differentiated cancer cells may acquire stem cell phenotypes. This means
that eradication of tumours will likely be achieved by the successful target-
ing of all cancer cells using a cocktail of drugs effective against all cancer cell
sub-populations and not only the stem cell type [457].
3.2 Brain Cancer Stem Cells
For many solid tumours within the CNS evidence in support of the cancer
stem cell hypothesis has emerged. In human glioblastoma, two separate stud-
ies from Bao et al [40] and Piccirillo et al [392] have separately tried to discern
the stem cell nature of this tumour, identified in a pioneering study by Singh
et al [458]. Glioblastomas are diffuse tumours that invade normal brain tissues
and frequently recur from focal masses after radiation, suggesting that only a
fraction of tumour cells is responsible for regrowth, supporting the cancer stem
cell hypothesis in solid tumours. The heterogeneity of glioblastoma starts at
63