Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array
| Autor: | Chao, Gao, Yan, Liu, Hongtao, Zhang, Yibing, Zhang, Michiko N, Fukuda, Angelina S, Palma, Radoslaw P, Kozak, Robert A, Childs, Motohiro, Nonaka, Zhen, Li, Don L, Siegel, Peter, Hanfland, Donna M, Peehl, Wengang, Chai, Mark I, Greene, Ten, Feizi |
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| Rok vydání: | 2014 |
| Předmět: |
Male
O-Glycome Designer Array Neoglycolipid Prostate Cancer Molecular Sequence Data Mucins Prostatic Neoplasms Glycobiology and Extracellular Matrices Glycolipid Carbohydrate Structure carbohydrates (lipids) Carbohydrate Microarray Carbohydrate Sequence Antigens Neoplasm Mass Spectrometry (MS) Cancer-associated Antigen Humans Glycan Array Antibody |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Background: F77 is a previously uncharacterized prostate cancer-associated antigen. Results: Using a microarray of sequence-defined glycolipids and neoglycolipids, mucin-O-glycan designer arrays, and mass spectrometry, we demonstrate that F77 antibody recognizes blood group H on 6-linked branches of poly-N-acetyllactosamine backbones. Conclusion: F77 antigen is expressed on glycolipids and on glycoprotein O-glycans. Significance: F77 antigen can now be explored rationally as a cancer biomarker. 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. |
| Databáze: | OpenAIRE |
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