title: Elevated levels of glycosylphosphatidylinositol (GPI) anchored proteins in plasma from human cancers detected by C. septicum alpha toxin.
abstract: The glycosylphosphatidylinositol (GPI) anchor is a glycan and lipid posttranslational modification added to proteins in the endoplasmic reticulum. Certain enzymes within the GPI biosynthetic pathway, particularly the subunits of the GPI transamidase, are elevated in various human cancers. Specific GPI anchored proteins, such as carcinoembryonic antigen and mesothelin, have been described as potential biomarkers for certain cancers; however, the overall levels of GPI anchored proteins present in plasma from cases of human cancers have not been evaluated. We have developed the use of a bacterial toxin known as alpha toxin from Clostridium septicum to detect GPI anchored proteins in vitro. In this study, we use alpha toxin to detect GPI anchored proteins present in plasma from cases of several types of human cancers. Our data indicate that human cancers with previously documented elevations of GPI transamidase subunits show increased alpha toxin binding to plasma from patients with these cancers, indicating increased levels of GPI anchored proteins. Furthermore, our results reveal very low levels of alpha toxin binding to plasma from patients with no malignant disease indicating few GPI anchored proteins are present. These data suggest that GPI anchored proteins present in plasma from these cancers represent biomarkers with potential use for cancer detection.
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Dolezal
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Shanterian
authors.initials: S
authors.lastname: Hester
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Kirby
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Nairn
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pierce
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Abbott
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000097:blood; D052557:Clostridium septicum / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism*; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000097:blood*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis; D011485:Protein Binding; D040901:Proteomics / Q000379:methods
chemical_list: D001427:Bacterial Toxins; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D009363:Neoplasm Proteins; C064270:hemolytic toxin, Clostridium septicum
keywords: Cancer; GPI-anchored proteins; GPIT; alpha toxin; human; plasma