NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature
| Autor: | Masashi Narita, Emma Kenney-Herbert, Colin Watts, Peter Collins, James W. Fawcett, Richard Grenfell, Sara Grazia Maria Piccirillo, M. Talal F. Al-Mayhani, Koichi Ichimura |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Cell Population Blotting Western Mice SCID Biology urologic and male genital diseases Flow cytometry Mice Cell Line Tumor medicine Biomarkers Tumor Animals Humans RNA Messenger Progenitor cell Antigens Clonogenic assay education Mitosis Cell Proliferation Oligonucleotide Array Sequence Analysis education.field_of_study Comparative Genomic Hybridization Mice Inbred ICR medicine.diagnostic_test Cell growth urogenital system Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Brain Flow Cytometry Molecular biology female genital diseases and pregnancy complications nervous system diseases Gene expression profiling Gene Expression Regulation Neoplastic medicine.anatomical_structure Phenotype Oncology nervous system Basic and Translational Investigations Cancer research Female Proteoglycans Neurology (clinical) Glioblastoma |
| Popis: | Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2- cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|