This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beier, D. Articles by Beier, C. P. Search for Related Content PubMed PubMed Citation Articles by Beier, D. Articles by Beier, C. P.

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

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]

This article has been cited by other articles:

				X. Fan and C. G. Eberhart Medulloblastoma Stem Cells J. Clin. Oncol., June 10, 2008; 26(17): 2821 - 2827. [Abstract] [Full Text] [PDF]

				P. B. Dirks Brain Tumor Stem Cells: Bringing Order to the Chaos of Brain Cancer J. Clin. Oncol., June 10, 2008; 26(17): 2916 - 2924. [Abstract] [Full Text] [PDF]

				B. Annabi, S. Rojas-Sutterlin, C. Laflamme, M.-P. Lachambre, Y. Rolland, H. Sartelet, and R. Beliveau Tumor Environment Dictates Medulloblastoma Cancer Stem Cell Expression and Invasive Phenotype Mol. Cancer Res., June 1, 2008; 6(6): 907 - 916. [Abstract] [Full Text] [PDF]

				A. Soeda, A. Inagaki, N. Oka, Y. Ikegame, H. Aoki, S.-i. Yoshimura, S. Nakashima, T. Kunisada, and T. Iwama Epidermal Growth Factor Plays a Crucial Role in Mitogenic Regulation of Human Brain Tumor Stem Cells J. Biol. Chem., April 18, 2008; 283(16): 10958 - 10966. [Abstract] [Full Text] [PDF]

				H. B. Huttner, P. Janich, M. Kohrmann, J. Jaszai, F. Siebzehnrubl, I. Blumcke, M. Suttorp, M. Gahr, D. Kuhnt, C. Nimsky, et al. The Stem Cell Marker Prominin-1/CD133 on Membrane Particles in Human Cerebrospinal Fluid Offers Novel Approaches for Studying Central Nervous System Disease Stem Cells, March 1, 2008; 26(3): 698 - 705. [Abstract] [Full Text] [PDF]

				F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment Genes & Dev., November 1, 2007; 21(21): 2683 - 2710. [Abstract] [Full Text] [PDF]