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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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3.2 Brain Cancer <strong>Stem</strong> <strong>Cells</strong> Introduction<br />

Figure 3.5: Glioblastoma treatment with BMPs. BMPs normally cause NS cells<br />

to differentiate into astrocytes. When used to treat isolated glioblastoma CD133 +<br />

cells, they weaken their tumourigenicity both in vitro and, when engrafted into mice,<br />

in vivo. The knowledge that a tumour retains a developmental hierarchy suggests<br />

that targeting different cell populations is a promising therapeutic strategy. Adapted<br />

from Dirks et al 2006 [121].<br />

because the true stem cells are probably a subpopulation <strong>of</strong> the CD133 + frac-<br />

tion, as demonstrated in the study by Bao et al by the death rates <strong>of</strong> mice<br />

after three months from treatment [123]. Another study attempting to eluci-<br />

date the role <strong>of</strong> CD133 was conducted in vivo on mice that were injected with<br />

100 to 1,000 uncultured malignant brain tumour cells purified by bead sorting<br />

for CD133 [459]. These CD133 + cells reproduced a phenotypical copy <strong>of</strong> the<br />

patient’s original tumour and were also heterogeneous, with only a minority<br />

<strong>of</strong> cells expressing CD133. This suggested differentiation in vivo, making dif-<br />

ferentiation therapy look like a real option for brain tumour treatment and<br />

denoting that brain tumours <strong>of</strong> different types are also functionally heteroge-<br />

neous for tumour-initiating ability [122].<br />

Several other studies have since then focused on the isolation <strong>of</strong> functional can-<br />

cer stem cell markers in different types and stages <strong>of</strong> brain tumours. In a study<br />

by Balenci et al [39], the mammalian IQ motif containing GTPase activating<br />

protein 1 (IQGAP1), considered to be a scaffolding protein at the intersection<br />

<strong>of</strong> several signaling pathways such as control <strong>of</strong> cell adhesion, polarization, di-<br />

rectional migration and neuronal motility, was found to be a reliable marker<br />

<strong>of</strong> Nestin + amplifying neural progenitors in rat brain. This protein is highly<br />

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