Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas
Autor: | Jesús M. Hernández-Rivas, Rogelio González-Sarmiento, Maria Perez-Caro, Oscar Blanco, Javier Ortiz, Manuel Sánchez-Martín, Francisco Javier González, J.A. Gómez-Moreta, Magdalena Sancho, Juan Luis García |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Angiogenesis Population Cell Biology lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Antigens CD Neurosphere Glioma Biomarkers Tumor Genetics medicine Humans AC133 Antigen RNA Messenger education neoplasms In Situ Hybridization Fluorescence Aged Glycoproteins Oligonucleotide Array Sequence Analysis 030304 developmental biology Comparative Genomic Hybridization 0303 health sciences education.field_of_study Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Middle Aged Flow Cytometry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Neural stem cell 3. Good health Gene expression profiling medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Stem cell Glioblastoma Peptides Research Article |
Zdroj: | BMC Cancer, Vol 10, Iss 1, p 454 (2010) Digital.CSIC. Repositorio Institucional del CSIC instname BMC Cancer |
ISSN: | 1471-2407 |
Popis: | 16 páginas, 8 figuras, 4 tablas.-- et al. [Background]: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. [Methods]: Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; [Results]: Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location and, the most importantly, the group discriminated by their proliferative potential; [Conclusions]: Primary glioblastomas could be sub-classified according to the properties of their CD133+ cells. The molecular characterization of these potential stem cell populations could be critical to find new therapeutic targets and to develop an effective therapy for these tumours with very dismal prognosis. Research in my group is supported by Ramon y Cajal Scientific Spanish Program, Junta de Castilla y León (SAN673/SA09/08) (SA093A08), and Department of Medicine from University of Salamanca. Dr. JL Garcia is supported by IESCyL foundation. |
Databáze: | OpenAIRE |
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