Biomedical Engineering Reference
In-Depth Information
Lineage Relationships Connecting Germinal
Regions to Brain Tumors
Nader Sanai and Arturo Alvarez-Buylla
Abstract Gliomas are a primary cancer of the brain and one of the most lethal
cancers known to man. Historically, the neoplastic transformation of fully
differentiated glia was widely assumed to be the only mechanism for glioma-
genesis. Astrocytes and oligodendrocytes, once thought to be the sole dividing
cells in the postnatal brain, were assumed to represent the cellular compartment
most susceptible to transformation. More recently, however, this hypothesis
has been challenged by the discovery of stem cell and progenitor populations
residing in the postnatal brain, which may themselves serve as an origin of brain
tumors. Phenotypic and behavioral similarities between gliomas and adult
neural stem cells raise the possibility that stem or progenitor cells can give rise
to gliomas. Possible candidate cells-of-origin include neuroepithelial cells, rad-
ial glia, astrocytic neural stem cells ('B cells'), transient amplifying precursors
('C cells') of the adult subventricular zone (SVZ), or oligodendrocyte progeni-
tor cells of the white matter. While a direct link has yet to be established between
any one of these cell types and tumor formation, the different cell lineages
arising from the ventricular and subventricular zone during development in
the adult may offer clues in deciphering the origin of various tumor subtypes,
including gliomas.
Contents
1 Development of Rodent Ventricular and Subventricular Zones . . . . . . . . . . . . . .
270
2 Unique Organization of the Human Subventricular Zone . . . . . . . . . . . . . . . . . . .
271
3 Glial Progenitors in the Subcortical White Matter . . . . . . . . . . . . . . . . . . . . . . . . .
272
4 Emergence of the Cancer Stem Cell Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . .
272
5 Susceptibility of Stem and Progenitor Cells to Transformation . . . . . . . . . . . . . . .
273
6 Shared Immature Expression Profiles Among Brain Tumors and Stem Cell Niches
274
6.1 Cytoskeletal Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
274
6.2 Tumor Suppressor Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
275
N. Sanai (*)
Institute for Regeneration Medicine and Department of Neurological Surgery,
University of California at San Francisco, 505 Parnassus Avenue, HSW 1201A,
San Francisco, CA 94143, USA
