title: Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies.
abstract: Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members related to the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family and are encoded by 10 genes in the human. They are secreted at high levels by placental syncytiotrophoblast into maternal blood during pregnancy, and are implicated in immunoregulation, thromboregulation, and angiogenesis. To determine whether PSGs are expressed in tumors, we characterized 16 novel monoclonal antibodies to human PSG1 and used 2 that do not cross-react with CEACAMs to study PSG expression in tumors and in the gastrointestinal (GI) tract using tissue arrays and immunohistochemistry. Staining was frequently observed in primary squamous cell carcinomas and colonic adenocarcinomas and was correlated with the degree of tumor differentiation, being largely absent from metastatic samples. Staining was also observed in normal oesophageal and colonic epithelium. PSG expression in the human and mouse GI tract was confirmed using quantitative RT-PCR. However, mRNA expression was several orders of magnitude lower in the GI tract compared to placenta. Our results identify a non-placental site of PSG expression in the gut and associated tumors, with implications for determining whether PSGs have a role in tumor progression, and utility as tumor biomarkers.
authors.affiliation: a School of Medicine , University College Cork , Ireland.
authors.forename: Aileen
authors.initials: A
authors.lastname: Houston
authors.affiliation: b School of Biochemistry and Cell Biology, University College Cork , Ireland.
authors.forename: John M
authors.initials: JM
authors.lastname: Williams
authors.affiliation: c Department of Histology and Embryology/Center for Proteomics , Faculty of Medicine, University of Rijeka , Croatia.
authors.forename: Tihana Lenac
authors.initials: TL
authors.lastname: Rovis
authors.affiliation: b School of Biochemistry and Cell Biology, University College Cork , Ireland.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Shanley
authors.affiliation: b School of Biochemistry and Cell Biology, University College Cork , Ireland.
authors.forename: Ronan T
authors.initials: RT
authors.lastname: O'Riordan
authors.affiliation: d Department of Life Sciences , Materials and Surface Science Institute and Stokes Institute, University of Limerick.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Kiely
authors.affiliation: b School of Biochemistry and Cell Biology, University College Cork , Ireland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ball
authors.affiliation: e Department of Pharmacology , Alimentary Pharmabiotic Center, University College Cork , Ireland.
authors.forename: Orla P
authors.initials: OP
authors.lastname: Barry
authors.affiliation: a School of Medicine , University College Cork , Ireland.
authors.forename: Jacquie
authors.initials: J
authors.lastname: Kelly
authors.affiliation: f Alimentary Pharmabiotic Center, University College Cork , Ireland.
authors.forename: Aine
authors.initials: A
authors.lastname: Fanning
authors.affiliation: f Alimentary Pharmabiotic Center, University College Cork , Ireland.
authors.forename: John
authors.initials: J
authors.lastname: MacSharry
authors.affiliation: g Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School , Jerusalem , Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.affiliation: h Institute of Anatomy, University Hospital, University Duisburg-Essen , Essen , Germany.
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.affiliation: c Department of Histology and Embryology/Center for Proteomics , Faculty of Medicine, University of Rijeka , Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.affiliation: b School of Biochemistry and Cell Biology, University College Cork , Ireland.
authors.forename: Tom
authors.initials: T
authors.lastname: Moore
mesh_terms: D000328:Adult; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology*; D011247:Pregnancy; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011268:Pregnancy-Specific beta 1-Glycoproteins
keywords: CEACAM; Carcinoembryonic antigen; Oesphagus; PSG1; colon; colonic adenocarcinoma; monoclonal antibody; placenta; pregnancy-specific glycoprotein; squamous cell carcinoma; squamous epithelium; trophoblast