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

Autor:	Gao C; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Liu Y; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, yan.liu2@imperial.ac.uk., Zhang H; the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082., Zhang Y; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Fukuda MN; the Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037., Palma AS; 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., Kozak RP; Ludger Ltd., Culham Science Centre, Oxfordshire OX14 3EB, United Kingdom., Childs RA; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Nonaka M; the Glycobiology Unit, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, La Jolla, California 92037., Li Z; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Siegel DL; the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082., Hanfland P; the Foundation of Haemotherapy Research, Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, D-53127 Bonn, Germany, and., Peehl DM; the Department of Urology, Stanford University School of Medicine, Stanford, California 94305., Chai W; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, w.chai@imperial.ac.uk., Greene MI; the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6082., Feizi T; From the Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom, t.feizi@imperial.ac.uk.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2014 Jun 06; Vol. 289 (23), pp. 16462-77. Date of Electronic Publication: 2014 Apr 21.
DOI:	10.1074/jbc.M114.558932
Abstrakt:	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. (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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