Hindawi Publishing Corporation Journal of Oncology Volume 2011, Article ID 314962, 16 pages doi:10.1155/2011/314962 Research Article Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres Valentina Caldera, 1 Marta Mellai, 1 Laura Annovazzi, 1 Angela Piazzi, 1, 2 Michele Lanotte, 3 Paola Cassoni, 4 and Davide Schiffer 1 1 Neuro-Bio-Oncology Center, Policlinico di Monza Foundation, University of Turin, 13100 Vercelli, Italy 2 Department of Medical Sciences, University of Piemonte Orientale, 28100 Novara, Italy 3 Department of Neuroscience, Neurosurgical Unit, University of Turin, 10124 Turin, Italy 4 Department of Biomedical Sciences and Human Oncology, University of Turin, 10124 Turin, Italy Correspondence should be addressed to Davide Schiffer, davide.schiffer@unito.it Received 14 February 2011; Revised 4 April 2011; Accepted 6 June 2011 Academic Editor: Dominic Fan Copyright © 2011 Valentina Caldera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Formation of neurospheres (NS) in cultures of glioblastomas (GBMs), with self-renewal, clonogenic capacities, and tumorigenicity following transplantation into immunodeficient mice, may denounce the existence of brain tumor stem cells (BTSCs) in vivo. In sixteen cell lines from resected primary glioblastomas, NS showed the same genetic alterations as primary tumors and the expression of stemness antigens. Adherent cells (AC), after adding 10% of fetal bovine serum (FBS) to the culture, were genetically different from NS and prevailingly expressed differentiation antigens. NS developed from a highly malignant tumor phenotype with proliferation, circumscribed necrosis, and high vessel density. Beside originating from transformed neural stem cells (NSCs), BTSCs may be contained within or correspond to dedifferentiated cells after mutation accumulation, which reacquire the expression of stemness antigens. 1. Introduction In leukemias, rare tumor cells show extensive proliferative and self-renewal potential and are responsible for main- taining the tumor clone [1]; similar cells were subsequently described in gliomas [2–4]. They were called brain tumor stem cells (BTSCs), believed to be responsible for tumor growth, recurrence and resistance to therapies and, suppos- edly, to derive from neural stem cells (NSCs) transformation and to be related to restricted unipotent or multipotent pro- genitors [5–7]. They share with NSCs antigenic properties of stemness, such as Nestin, Musashi-1, CD133, and SOX2 expression [8]; it has been suggested to better identify them on the basis of their functional competence than as cell types [9]. A derivation from dedifferentiated tumor cells that re- acquire stem cell-like properties has also been hypothesized [3, 10, 11]. Beside common antigenic properties with NSCs, BTSCs share genetic properties with primary tumor cells. Their exis- tence in tumors is indirectly demonstrated by the generation, from tumor samples put in culture, of neurospheres (NS) and, by adding 10% of fetal bovine serum (FBS), of adherent cells (AC) with different capacities of self-renewal, differenti- ation, clonogenicity, and tumorigenicity. The demonstration of BTSCs in vitro may be influenced by the methodological procedures employed and may have different expression mo- dalities [12, 13]. For example, using N29 and N32 tumor models, it has been demonstrated that NS formation is not necessary to enrich for tumorigenic cells, due to the fact that AC can display high clonogenicity in vitro, tumorigenicity in vivo, and high expression of CD133 and Nestin [14]. Recently, two transcription factors have been proposed as putative markers of stemness: sex determining region of Y chromosome (Sry)-related high mobility group box2 (SOX2) and repressor element-1 silencing transcription/neuron-re- strictive silencer factor (REST/NRSF). SOX2 belongs to a family of transcription factors expressed in the central nerv- ous system (CNS) at early stages of development [15] and it is expressed in malignant gliomas at both mRNA and