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
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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