Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.2 Brain Cancer Stem Cells Introduction
tially differentiated down the lineage that characterised the original tumour
phenotype of the patient, losing the expression of Nestin and CD133 and gain-
ing the markers of differentiation that reflected the immunophenotype of the
original tumour [458]. This is a common finding amongst astrocytoma cells
that are grown as neurospheres, which differentiate into GFAP + astrocytes,
and glioblastoma cells, which instead differentiate into GFAP + astrocytes as
well as TUBB3 neurons, suggesting that the tumours derive from a cell with
multi-lineage differentiation capacity, i.e. a stem cell, and not a dedifferenti-
ated astrocyte as previously thought [122]. When tumour cell cultures from
the 14 pediatric tumours were sorted for CD133 expression, CD133 + tumour
cells showed growth as non-adherent tumour spheres with continuous expan-
sion of their cell population, while CD133 - cells adhered to the culture dishes
without showing proliferation and not forming spheres, demonstrating that
the stem cell properties resided in the CD133 + fraction [458]. With this study,
Singh et al demonstrated that the CD133 marker can identify an exclusive
subpopulation of brain tumour cells with NS cell activity, with three pieces of
evidence supporting this view:
1. CD133 + cells generated clusters of clonally derived cells that resembled
neurospheres, termed "tumour spheres";
2. CD133 + cells were capable of constant self-renewal, as well as prolifera-
tion;
3. CD133 + cells differentiated to recapitulate the phenotype of the tumour
from which they were derived.
It must be noted that self-renewal and proliferation differ because the former is
a cell division that must involve a cell fate decision, so that at least one of the
two daughter cells retains the full stem cell potential of the parent cell (Fig 3.2).
Exploring the molecular mechanisms involved in cell fate decisions of brain tu-
mour stem cell divisions could have important implications in understanding
clonal expansion and maintenance of these tumours [122]. Although cancer-
initiating abilities clearly reside in the CD133 + fraction, not every CD133 +
cell is capable of initiating sphere formation in vitro, demonstrating that not
every CD133 + cell has stem cell properties [122] and implying the existence of
a hierarchy, which will be functionally elucidated as more surface markers for
NS cells emerge and additional subpopulations are identified [458].
65