Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.1 The Cancer Stem Cell Hypothesis Introduction
of origin, cancer stem cells give rise to tumours that phenotypically resemble
their origin, either by morphology or by expression of tissue-specific genes.
However, what distinguishes cancerous tissue from normal tissue is the loss
of homeostatic mechanisms that maintain normal cell numbers, and much of
this regulation normally occurs at the stem cell level. The cancer stem cell
hypothesis raises the important experimental implication that if a population
of biologically unique cancer stem cells exists, then tumour cells lacking stem
cell properties will not be able to initiate self-propagating tumours, regardless
of their differentiation status or proliferative capacity, which has an impact
on the experimental definition of cancer stem cell. Furthermore, the cancer
stem cell hypothesis raises a clinical implication that curative therapy will re-
quire complete elimination of the cancer stem cell population, since patients
who show an initial response to treatment may ultimately relapse if even a
small number of cancer stem cells survive. On the other hand, targeted ther-
apies that eliminate the cancer stem cell population offer the potential for a
cure [486].
The concept of cancer stem cell initially arose from the observation that cancer
tissues resembled developing tissues and self-renewal mechanisms were com-
mon to cancer cells and stem cells. The definitive demonstration of cancer stem
cells in human neoplasia was first made in 1994 in leukemia [122], a non-solid
tumour found harbouring a stem cell hierarchy pattern, in which a minority
of cells within the leukemic population possessed extensive proliferation and
self-renewal capacity not found, however, in the rest of the leukemic cells.
The putative cancer stem cells in leukemia were isolated and characterised
on the basis of their phenotypical similarities to normal hematopoietic stem
cells. The principle of uncovering significant similarities between putative can-
cer stem cells and normal stem cells, was then extended to solid tumours, first
in breast cancer then in brain cancer, although normal stem cells, their differ-
entiation hierarchy and markers that identify them, are not well characterized
in most solid organs. Since then, other tissues in which the connection be-
tween stem cells and cancer has been found are mammary gland [15,288,289],
gut [177,395,414], skin [75], bladder [89] and prostate [103] .
So far, cancer stem cells have been defined on the basis of their ability to seed
tumours in animal hosts, to self-renew and to generate non-cancer stem cell
differentiated progeny. Accordingly, the number of cancer stem cells within
a population of cancer cells can be measured by the number of cells that are
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