Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array.
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.
['Gao|Chao|C|', 'Liu|Yan|Y|', 'Zhang|Hongtao|H|', 'Zhang|Yibing|Y|', 'Fukuda|Michiko N|MN|', 'Palma|Angelina S|AS|', 'Kozak|Radoslaw P|RP|', 'Childs|Robert A|RA|', 'Nonaka|Motohiro|M|', 'Li|Zhen|Z|', 'Siegel|Don L|DL|', 'Hanfland|Peter|P|', 'Peehl|Donna M|DM|', 'Chai|Wengang|W|', 'Greene|Mark I|MI|', 'Feizi|Ten|T|']
D000951:Antigens, Neoplasm D002240:Carbohydrate Sequence D006801:Humans D008297:Male D008969:Molecular Sequence Data D009077:Mucins D011471:Prostatic Neoplasms
Cancer-associated Antigen O-Glycome Designer Array Antibody Prostate Cancer Glycolipid Carbohydrate Microarray Carbohydrate Structure Glycan Array Mass Spectrometry (MS) Neoglycolipid