The
oligosaccharide structures of
prostate specific antigen (PSA) are expected to be useful in discriminating
prostate cancer from benign conditions both accompanied by increased serum PSA levels. A large proportion of PSA forms a covalent complex with a
glycoprotein,
alpha(1)-antichymotrypsin, in human blood. In the present study, the
glycan profiles of free and complexed forms of PSA from
cancer patient serum and of seminal plasma PSA were compared by analyzing the
glycopeptides obtained by lysylendopeptidase digestion of the electrophoretically separated PSA with mass spectrometry. The profiles of the PSA N-
glycans from the free and complexed molecules were quite similar to each other and consisted of fucosylated biantennary
oligosaccharides as the major class. They were mostly sialylated, and a considerable
sialic acid fraction was alpha2,3-linked as determined by Streptococcus pneumoniae
neuraminidase digestion of the
glycopeptides. In the seminal plasma PSA, high-
mannose and hybrid types of
oligosaccharides were predominant, and the
sialic acids attached to the latter as well as to biantennary oligosaccahrides were exclusively alpha2,6-linked because they were removed by Arthrobacter ureafaciens
neuraminidase but resistant to S. pneumoniae
neuraminidase. Complex-type
oligosaccharides from other sources were found in the seminal plasma sample, indicating that analysis of released
glycans carries a risk of being misleading. The results suggest that identification of alpha2,3-linked
sialic acids on PSA potentially discriminates malignant from benign conditions, if the analysis is applied to
oligosaccharides specifically attached to the N-glycosylation site of PSA in either a free or a complexed form in the serum.