The presence of stem cell characteristics in glioma cells raises the

The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers including the transcription factors Oct4 Sox2 Nanog and Klf4. In line with this obtaining in high grade gliomas mesodermal- and endodermal-specific transcription factors were detected together with neural proteins a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell characteristics could only be detected in solid tumors and observations based on studies and xenograft transplantations in mice imply that this presence is dependent around the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell characteristics in malignant human gliomas and show that stem cell regulatory factors may provide significant targets for therapeutic strategies. Introduction The identification of tumor cells with stem cell properties supports the idea that a subpopulation of malignancy cells is responsible for the initiation growth and recurrence of tumors. Apparent similarities with non-transformed stem Mouse monoclonal antibody to PRMT1. This gene encodes a member of the protein arginine N-methyltransferase (PRMT) family. Posttranslationalmodification of target proteins by PRMTs plays an important regulatory role in manybiological processes, whereby PRMTs methylate arginine residues by transferring methyl groupsfrom S-adenosyl-L-methionine to terminal guanidino nitrogen atoms. The encoded protein is atype I PRMT and is responsible for the majority of cellular arginine methylation activity.Increased expression of this gene may play a role in many types of cancer. Alternatively splicedtranscript variants encoding multiple isoforms have been observed for this gene, and apseudogene of this gene is located on the long arm of chromosome 5 cells including high self-renewal capacity and the ability to generate differentiated progeny of several cellular lineages have lead to the proposal that stem cell-like malignancy cells may either originate from adult undifferentiated stem and progenitor CEP-18770 cells or that these properties are being expressed as an effect of the genetic alterations which drive tumorigenicity [1]. Regardless the association of stem cell characteristics with malignancy pathogenesis motivates a further characterization of stem cell related signatures in tumors and a better description of molecular similarities and differences in comparison with non-transformed stem cells. Glioma is the most common form of main tumors of the central nervous system (CNS) in adults [1]. Based on histopathological characteristics this type of tumor can be divided into four malignancy grades (grade I-IV World Health Business) where grade IV tumors glioblastoma multiforme are the most malignant with no curative measures available [1] [2] [3]. Several reports have exhibited that gliomas harbor cells with stem cell-like features including the ability to generate progeny of the neural and glial lineages as well as to mediate the recurrence of tumors [4]. For example the cell-surface protein CD133 (or prominin-1) which is usually expressed by stem cells of the human brain [5] has also been used to enrich for stem cells in gliomas [4] [6] [7] and has been considered as a marker for cells with enhanced tumorigenicity [4] [6] [7]. The HMG-box transcription factor Sox2 and the bHLH protein Olig2 constitute additional examples of factors commonly expressed by glioma cells and stem cells of CEP-18770 the embryonic and adult brain [8] [9] [10]. Interestingly both Sox2 and Olig2 have been ascribed important functions in maintaining self-renewing stem cells in the CNS [10] [11] and this activity appears at least in part to be conserved in gliomas [8] [10] [12] [13]. For instance loss of Sox2 function limits the self-renewing capacity [12] of human glioma cells and reduces their tumor-inducing potential when transplanted into the rodent brain [8]. Hence transcription factors with important regulatory functions in non-transformed stem cells are both expressed and possess comparable vital functions in the maintenance of lineage-related stem and progenitor cells in gliomas. However the gene expression profile in gliomas may not necessarily mirror its cell of origin. For example the transcription factor Oct4 which has an important role in maintaining embryonic stem (ES) cells in a self-renewing and pluripotent state [14] is not expressed in the adult brain but can be detected in high grade gliomas [15]. Moreover downstream targets of Oct4 have been reported CEP-18770 to be more frequently over-expressed in high grade gliomas compared with lower grade tumors [16]. In the adult mice misexpression of Oct4 in epithelial tissues results in dysplasia caused by a CEP-18770 block in progenitor differentiation [17]. Thus the reactivation of stem cell genes such as Oct4 may contribute to the enhanced malignancy of high grade gliomas. It is interesting that several transcriptional networks with vital functions in neural and other stem cell populations appear to be expressed in gliomas [8] [10] [16]. Their necessity for the maintenance of self-renewing stem and progenitor cells raises the possibility that these.