title: Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array.
abstract: Monoclonal antibody F77 was previously raised against human prostate cancer cells and has been shown to recognize a carbohydrate antigen, but the carbohydrate sequence of the antigen was elusive. Here, we make multifaceted approaches to characterize F77 antigen, including binding analyses with the glycolipid extract of the prostate cancer cell line PC3, microarrays with sequence-defined glycan probes, and designer arrays from the O-glycome of an antigen-positive mucin, in conjunction with mass spectrometry. Our results reveal F77 antigen to be expressed on blood group H on a 6-linked branch of a poly-N-acetyllactosamine backbone. We show that mAb F77 can also bind to blood group A and B analogs but with lower intensities. We propose that the close association of F77 antigen with prostate cancers is a consequence of increased blood group H expression together with up-regulated branching enzymes. This is in contrast to other epithelial cancers that have up-regulated branching enzymes but diminished expression of H antigen. With knowledge of the structure and prevalence of F77 antigen in prostate cancer, the way is open to explore rationally its application as a biomarker to detect F77-positive circulating prostate cancer-derived glycoproteins and tumor cells.
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, yan.liu2@imperial.ac.uk.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: the Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, the Department of Chemistry, New University, 2829-516 Lisbon, Portugal.
authors.forename: Angelina S
authors.initials: AS
authors.lastname: Palma
authors.affiliation: Ludger Ltd., Culham Science Centre, Oxfordshire OX14 3EB, United Kingdom.
authors.forename: Radoslaw P
authors.initials: RP
authors.lastname: Kozak
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Childs
authors.affiliation: the Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nonaka
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082.
authors.forename: Don L
authors.initials: DL
authors.lastname: Siegel
authors.affiliation: the Foundation of Haemotherapy Research, Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, D-53127 Bonn, Germany, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Hanfland
authors.affiliation: the Department of Urology, Stanford University School of Medicine, Stanford, California 94305.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Peehl
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, w.chai@imperial.ac.uk.
authors.forename: Wengang
authors.initials: W
authors.lastname: Chai
authors.affiliation: the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Greene
authors.affiliation: From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, t.feizi@imperial.ac.uk.
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry*; D002240:Carbohydrate Sequence; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D009077:Mucins
keywords: Antibody; Cancer-associated Antigen; Carbohydrate Microarray; Carbohydrate Structure; Glycan Array; Glycolipid; Mass Spectrometry (MS); Neoglycolipid; O-Glycome Designer Array; Prostate Cancer
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