Identification of novel tumor-associated cell surface sialoglycoproteins in human glioblastoma tumors using quantitative proteomics
| Autor: | Su Wang, Denis Loyaux, Michael A. Smith, Catherine Déon, Jean-Claude Guillemot, Steven A. Goldman, Sébastien Roudières, Philippe Fabre, Paul R. August, Fréderique Guette, Pascual Ferrara, François Autelitano, Qinggong Ping, Romane Auvergne, Vasudeo Badarinarayana, Sridaran Natesan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Proteomics
Male Pathology Glycosylation Cell Glycobiology Cancer Treatment lcsh:Medicine Biochemistry Mass Spectrometry Analytical Chemistry Pregnancy Basic Cancer Research Medicine and Health Sciences N-Linked Glycoproteins Sialoglycoproteins lcsh:Science Neurological Tumors chemistry.chemical_classification Cancer Drug Discovery Multidisciplinary Brain Neoplasms Middle Aged Chemistry Protein Transport medicine.anatomical_structure Neurology Oncology Liquid Chromatography-Tandem Mass Spectrometry Physical Sciences Female Research Article Adult medicine.medical_specialty Immunology Quantitative proteomics Biology Antibody Therapy Cell surface receptor Glioma Cancer Detection and Diagnosis medicine Humans Biotinylation Glycoproteins Aged Gene Expression Profiling lcsh:R Biology and Life Sciences medicine.disease N-Acetylneuraminic Acid Gene expression profiling Membrane protein chemistry Clinical Immunology lcsh:Q Glioblastoma Glycoprotein Glioblastoma Multiforme |
| Zdroj: | PLoS ONE, Vol 9, Iss 10, p e110316 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Glioblastoma multiform (GBM) remains clinical indication with significant "unmet medical need". Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG) cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR) in combination with label-free quantitative mass spectrometry (LFQ-MS) to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs). We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72%) are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells. |
| Databáze: | OpenAIRE |
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