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Cancer Research 67, 4010-4015, May 1, 2007. doi: 10.1158/0008-5472.CAN-06-4180
© 2007 American Association for Cancer Research

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Priority Reports

CD133+ and CD133 Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles

Dagmar Beier1, Peter Hau1, Martin Proescholdt3, Annette Lohmeier1, Jörg Wischhusen5, Peter J. Oefner4, Ludwig Aigner2, Alexander Brawanski3, Ulrich Bogdahn1 and Christoph P. Beier1

1 Laboratory of Neurooncology and 2 VW-Junior Group, Department of Neurology, 3 Department of Neurosurgery, and 4 Institute of Functional Genomics, University of Regensburg, Regensburg, Germany; and 5 Interdisciplinary Center for Clinical Research, Junior Research Group "Tumor Progression and Immune Escape", Clinics for Gynecology and Obstetrics, University of Würzburg, Würzburg, Germany

Requests for reprints: Christoph P. Beier, Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany. Phone: 49-941-941-3258; Fax: 49-941-941-3292; E-mail: Christoph.Beier{at}gmx.de.

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)–derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell–like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133+ subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133 tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133 glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133+ CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133 tumor cells with apparent stem cell–like properties but distinct molecular profiles and growth characteristics in vitro and in vivo. [Cancer Res 2007;67(9):4010–5]




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Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2007 by the American Association for Cancer Research.