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J Biol Chem. 2014 Jun 6;289(23):16462-77. doi: 10.1074/jbc.M114.558932. Epub 2014 Apr 21.

Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array.

Author information

1
From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom.
2
From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, yan.liu2@imperial.ac.uk.
3
the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082.
4
the Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
5
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.
6
Ludger Ltd., Culham Science Centre, Oxfordshire OX14 3EB, United Kingdom.
7
the Foundation of Haemotherapy Research, Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, D-53127 Bonn, Germany, and.
8
the Department of Urology, Stanford University School of Medicine, Stanford, California 94305.
9
From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, w.chai@imperial.ac.uk.
10
From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, t.feizi@imperial.ac.uk.

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.

KEYWORDS:

Antibody; Cancer-associated Antigen; Carbohydrate Microarray; Carbohydrate Structure; Glycan Array; Glycolipid; Mass Spectrometry (MS); Neoglycolipid; O-Glycome Designer Array; Prostate Cancer

PMID:
24753245
PMCID:
PMC4047413
DOI:
10.1074/jbc.M114.558932
[Indexed for MEDLINE]
Free PMC Article

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