Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer array [Immunology]
April 21st, 2014 by Gao, C., Liu, Y., Zhang, H., Zhang, Y., Fukuda, M. N., Palma, A. S., Kozak, R. P., Childs, R. A., Nonaka, M., Li, Z., Siegel, D. L., Hanfland, P., Peehl, D. M., Chai, W., Greene, M. I., Feizi, T.
Monoclonal antibody F77 was previously raised against human prostate cancer cells and 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 bind also to the 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 upregulated branching enzymes. This is in contrast to other epithelial cancers which have upregulated 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.