Affiliations: [a] Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA | [b] Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA | Biochemistry and Bio-related Chemistry Branch Pharmacology, Physiology, and Biological Chemistry Division NIGMS, NIH
Correspondence:
[*]
Corresponding author: Karen L. Abbott, Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. E-mail: [email protected].
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.
Keywords: Cancer, plasma, GPI-anchored proteins, GPIT, alpha toxin, human
