The Role of Glycosylation in the Biological Activities of Prostate Specific Antigen
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Background: PSA is a biomarker for diagnosis and management of prostate cancer (CaP). It is known to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies, however, the physiological role of PSA in the progression of CaP still remains unknown. Hyper-glycosylation of proteins, including PSA, is a fundamental characteristic of aggressive cancers. The aim of this study is to study the effects of protein glycosylation and deglycosylation (i.e. glycan removal) in order to understand significant local and global changes in the biological activity of PSA. Methods: f-PSA was purified from human seminal plasma by a simple two-step column chromatography method. Confluent monolayers of endothelial cell line, HUVEC and prostate cancer epithelial cell line, PC-3M were treated with native glycosylated f-PSA and deglycosylated f-PSA in various in-vitro biological assays to determine the difference between glycosylated and deglycosylated. q-PCR, matrigel, and cell migratory studies were carried out to determine the changes in expression of various genes that are known to regulate tumor growth and metastasis. Results: Equimolar concentrations of native glycosylated f-PSA and deglycosylated f-PSA had similar physiological effects on PC-3M and HUVEC cells inhibiting the gene expression of pro-angiogenic and pro-metastatic growth factors such as VEGF, KDR, FAK, and TWIST. f-PSA both glycosylated and deglycosylated has an inhibitory effect on tube formation in HUVEC cells and the migratory property of both PC3-M and HUVEC cells. Discussion: Our data provides compelling evidence that native glycosylated f-PSA and deglycosylated affects the expression of growth factors and genes involved in migration and metastasis in both epithelial and vasculature cells in an analogous manner. The study supported the hypothesis that the PSA glyco-moiety structure is independent of its innate anti-angiogenic and anti-tumorgenic properties.