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Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.

Original publication

DOI

10.1158/0008-5472.CAN-07-0183

Type

Journal article

Journal

Cancer Res

Publication Date

15/06/2007

Volume

67

Pages

5727 - 5736

Keywords

AC133 Antigen, Adult, Animals, Antigens, CD, Astrocytes, Blotting, Western, Brain Neoplasms, Embryonic Stem Cells, Ependyma, Epithelial Cells, Flow Cytometry, Fluorescent Antibody Technique, Glioblastoma, Glycoproteins, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neoplastic Stem Cells, Neuroglia, Peptides, Prosencephalon