Biomedical Engineering Reference
In-Depth Information
subpopulation of B cells within the adult SVZ constitute a large population
of dividing progenitors in the adult brain. EGF-mediated stimulation of this
population prevents C cell differentiation and induces their migration, leading
to an infiltrative phenotype comparable to that seen among high-grade gliomas
(Doetsch et al. 2002a).
A population of platelet-derived growth factor (PDGF)+ type B cells have
also been identified in the adult rodent SVZ. These cells can give rise to both
neurons and oligodendrocytes in vivo (Jackson et al. 2006). With excessive
PDGF activation, the rodent SVZ arrests neuroblast production, induces
SVZ cellular proliferation, and creates areas of hyperplasia with features of
early glioma formation (Jackson et al. 2006). This behavior change represents a
potential link between these PDGFR+ type B cells and the early changes
associated with tumor initiation. Considering the frequency of PDGFR over-
expression among both low- and high-grade gliomas, these findings raise the
possibility that transformed SVZ type B cells could serve as a source of gliomas
and primary glioblastomas.
6.4 Vascular Niches
A strong association exists between vascular and neurogenic niches in adult
germinal regions (Gilbertson and Rich 2007; Palmer et al. 2000; Tavazoie et al.
2008). Gliomas are typically hyper-vascularized and associated with neovascu-
lar beds (Fischer et al. 2005). Not only are stem and progenitor cells typically
clustered around or in contact with blood vessels (Palmer et al. 2000), but
vascular endothelial growth factor (VEGF) and its receptors are expressed by
neurospheres derived from rodent SVZ (Knizetova et al. 2008). VEGF has also
been implicated in glioma growth and it is secreted by glioma cells that act on
tumor endothelial cells expressing VEGF receptors (Jain et al. 2007). Similarly,
cancer stem cells isolated from gliomas also generate markedly elevated levels of
VEGF (Bao et al. 2006a). Interestingly, type B cells in the rodent are known to
extend basal processes that specifically contact blood vessel endothelia (Mirzadeh
et al. 2008). Taken together, these data suggest that similar microenvironments
promote both stem/progenitor cell growth and tumorigenesis and also that
targeting proangiogenic factors may be a therapeutic strategy against the
putative cancer stem cell fraction.
6.5 Transcription Factors
If neural stem cells are the source of tumor initiation, their progression toward a
tumorigenic state may be achieved through the operation of abnormal develop-
mental programs (Wechsler-Reya and Scott 2001). Multiple developmental
signaling pathways associated with normal stem/progenitor cell function may
