title: Glycomic analysis of membrane glycoproteins with bisecting glycosylation from ovarian cancer tissues reveals novel structures and functions.
abstract: Biomarkers capable of detecting and targeting epithelial ovarian cancer cells for diagnostics and therapeutics would be extremely valuable. Ovarian cancer is the deadliest reproductive malignancy among women in the U.S., killing over 14 000 women each year. Both the lack of presenting symptoms and high mortality rates illustrate the need for earlier diagnosis and improved treatment of this disease. The glycosyltransferase enzyme GnT-III encoded by the Mgat3 gene is responsible for the addition of GlcNAc (N-acetylglucosamine) to form bisecting N-linked glycan structures. GnT-III mRNA expression is amplified in ovarian cancer tissues compared with normal ovarian tissue. We use a lectin capture strategy coupled to nano-ESI-RPLC-MS/MS to isolate and identify the membrane glycoproteins and unique glycan structures associated with GnT-III amplification in human ovarian cancer tissues. Our data illustrate that the majority of membrane glycoproteins with bisecting glycosylation are common to both serous and endometrioid histological subtypes of ovarian cancer, and several have been reported to participate in signaling pathways such as Notch, Wnt, and TGFβ.
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia , 315 Riverbend Road, Athens, Georgia 30602, United States.
authors.forename: Heba
authors.initials: H
authors.lastname: Allam
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aoki
authors.forename: Benedict B
authors.initials: BB
authors.lastname: Benigno
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.forename: Michael
authors.initials: M
authors.lastname: Tiemeyer
authors.forename: Karen L
authors.initials: KL
authors.lastname: Abbott
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D054794:Glycomics / Q000379:methods; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase
keywords: biomarkers; bisecting N-linked glycans; glycoproteins; human tissue; mass spectrometry; ovarian cancer