Neuronatin in a subset of glioblastoma multiforme tumor progenitor cells is associated with increased cell proliferation and shorter patient survival
Autor: | David S. Xu, Russell R. Lonser, Cheng S. Lee, Elisabeth Bründl, Zhengping Zhuang, Robert J. Weil, Alexander Brawanski, Chunzhang Yang, Xueping Fang, Martin Proescholdt |
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Rok vydání: | 2012 |
Předmět: |
Proteomics
Pathology Biological Markers/metabolism Cellular differentiation Cancer Treatment 610 Medizin Nerve Tissue Proteins/metabolism lcsh:Medicine Kaplan-Meier Estimate Signal transduction Molecular cell biology Tandem Mass Spectrometry Basic Cancer Research Signaling in Cellular Processes Protein Isoforms Glioblastoma/metabolism U87 lcsh:Science Neurological Tumors ddc:610 Multidisciplinary Signaling cascades Oncology Neoplastic Stem Cells Medicine Stem cell Proteomics/methods Protein Isoforms/metabolism Research Article Drugs and Devices medicine.medical_specialty MAPK signaling cascades Drug Research and Development Brain tumor Nerve Tissue Proteins Biology Neoplastic Stem Cells/metabolism Diagnostic Medicine Glioma medicine Humans Progenitor cell Cell Proliferation Medulloblastoma lcsh:R Cancers and Neoplasms Membrane Proteins Chemotherapy and Drug Treatment medicine.disease nervous system diseases Cancer research Neuronatin lcsh:Q Membrane Proteins/metabolism Isoelectric Focusing Glioblastoma Biomarkers Glioblastoma Multiforme General Pathology Chromatography Liquid |
Zdroj: | PLoS ONE, Vol 7, Iss 5, p e37811 (2012) PLoS ONE |
DOI: | 10.5283/epub.29175 |
Popis: | Glioblastoma multiforme is the most common and malignant primary brain tumor. Recent evidence indicates that a subset of glioblastoma tumor cells have a stem cell like phenotype that underlies chemotherapy resistance and tumor recurrence. We utilized a new "multidimensional" capillary isoelectric focusing nano-reversed-phase liquid chromatography platform with tandem mass spectrometry to compare the proteomes of isolated glioblastoma tumor stem cell and differentiated tumor cell populations. This proteomic analysis yielded new candidate proteins that were differentially expressed. Specifically, two isoforms of the membrane proteolipid neuronatin (NNAT) were expressed exclusively within the tumor stem cells. We surveyed the expression of NNAT across 10 WHO grade II and III gliomas and 23 glioblastoma (grade IV) human tumor samples and found NNAT was expressed in a subset of primary glioblastoma tumors. Through additional in vitro studies utilizing the U87 glioma cell line, we found that expression of NNAT is associated with significant increases in cellular proliferation. Paralleling the in vitro results, when NNAT levels were evaluated in tumor specimens from a consecutive cohort of 59 glioblastoma patients, the presence of increased levels of NNAT were found to be a an independent risk factor (P = 0.006) for decreased patient survival through Kaplan-Meier and multivariate analysis. These findings indicate that NNAT may have utility as a prognostic biomarker, as well as a cell-surface target for chemotherapeutic agents. |
Databáze: | OpenAIRE |
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