title: Identification of novel tumor-associated cell surface sialoglycoproteins in human glioblastoma tumors using quantitative proteomics.
abstract: 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.
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Autelitano
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Loyaux
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roudières
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Déon
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Guette
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fabre
authors.affiliation: ALS Therapy Development Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Qinggong
authors.initials: Q
authors.lastname: Ping
authors.affiliation: Department of Neurology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Romane
authors.initials: R
authors.lastname: Auvergne
authors.affiliation: Sanofi Tucson Research Center, Oro Valley, Arizona, United States of America.
authors.forename: Vasudeo
authors.initials: V
authors.lastname: Badarinarayana
authors.affiliation: Sanofi Tucson Research Center, Oro Valley, Arizona, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Smith
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Guillemot
authors.affiliation: Department of Neurology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
authors.affiliation: Sanofi US, Cambridge, Massachusetts, United States of America.
authors.forename: Sridaran
authors.initials: S
authors.lastname: Natesan
authors.affiliation: Sanofi-Aventis Recherche & Développement, Centre de Toulouse, Toulouse, France.
authors.forename: Pascual
authors.initials: P
authors.lastname: Ferrara
authors.affiliation: Sanofi Tucson Research Center, Oro Valley, Arizona, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: August
mesh_terms: D000328:Adult; D000368:Aged; D019921:Biotinylation; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011247:Pregnancy; D021381:Protein Transport; D040901:Proteomics / Q000379:methods*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012795:Sialoglycoproteins; D019158:N-Acetylneuraminic Acid