Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy

Abstract

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

Glycan Characterization of PSA 2-DE Subforms from Serum and Seminal Plasma

“…In the same study, we observed a different proportion of alpha 2-3 linked sialic acid in the PSA present in patients, which was decreased in relation to that from healthy seminal plasma (15 vs. 25%) (Tabares et al, 2006). However, our present results are more consistent with the observations made by other authors (Ohyama et al, 2004;Tajiri et al, 2008).…”

“…These changes in this major subform may be considered representative of the whole PSA, as F3 accounts for 50-70% of all PSA subforms. The percentage of alpha 2-3 sialic acid in seminal plasma PSA was consistent with our previous analyses (25%) (Tabares et al, 2006) and with studies by Ohyama and coworkers (*20%) (Ohyama et al, 2004). In the same study, we observed a different proportion of alpha 2-3 linked sialic acid in the PSA present in patients, which was decreased in relation to that from healthy seminal plasma (15 vs. 25%) (Tabares et al, 2006).…”

“…In fact, secreted glycoproteins can reflect the changes in glycosylation pattern that usually take place on the tumor cells surface (Peracaula, 2007;Varki et al, 2008). Several authors have described modifications in the sialylation pattern of PSA derived from malignant origins compared with that from healthy individuals (Huber et al, 1995;Ohyama et al, 2004;Peracaula et al, 2003;Tabares et al, 2006). Sialic acid is a negatively charged carbohydrate.…”

Differential expression of the α2,3-sialic acid residues in breast cancer is associated with metastatic potential

“…the content of sialic acid have been elevated on some malignant tumor cells, a positive correlation between cell metastatic potential and total sialic acid content has been reported in many types of tumors. Most of these studies suggested that high level of sialylation may contribute to invasion and metastasis (17)(18)(19). the tumor dissemination is a multistep process involving aberrant biological behavior of tumor cells, such as adhesion, migration and invasion.…”

Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity

“…Earlier studies observed that a large portion of KLK3 from plasma of prostate cancer patients was non-glycosylated, whereas malignant tumor cells generate KLK3 with more antennae than the common biantennary N-glycan of normal KLK3 (Barak et al, 1989;Prakash and Robbins, 2000). Also, the glycosylation of prostate cancer KLK3 was reduced in benign prostate hyperplasia (BPH) and exhibited a different composition (Basu et al, 2003;Ohyama et al, 2004) KLK3 from prostate tumor cell lines shows an altered sugar composition, with a significant lack of sialic acid in the N-glycan tree (Peracaula et al, 2003). Seemingly, differences exist in fucosylation and sialylation of KLK3 from prostate cancer patients, although they do not appear to be sufficient for reliable prognosis of the disease (Tabares et al, 2006(Tabares et al, , 2007.…”