Glycomic Characterization of Prostate-Specific Antigen and Prostatic Acid Phosphatase in Prostate Cancer and Benign Disease Seminal Plasma Fluids

Department of Microbiology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
Journal of Proteome Research (Impact Factor: 4.25). 02/2009; 8(2):620-30. DOI: 10.1021/pr8007545
Source: PubMed


Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are glycoproteins secreted by prostate epithelial cells, and have a long clinical history of use as serum biomarkers of prostate cancers. These two proteins are present at significantly higher concentrations in seminal plasma, making this proximal fluid of the prostate a good source for purifying enough protein for characterization of prostate disease associated changes in glycan structures. With the use of seminal fluid samples representative of normal control, benign prostatic disease and prostate cancers, PAP and PSA were enriched by thiophilic absorption chromatography. Released N-linked glycan constituents from both proteins were analyzed by a combination of normal phase HPLC and MALDI-TOF spectrometry. For PSA, 40 putative glycoforms were determined, and 21 glycoforms were determined for PAP. PAP glycans were further analyzed with a hybrid triple quadrupole/linear ion trap mass spectrometer to assign specific glycoform classes to each of the three N-linked sites. The glycans identified in these studies will allow for more defined targeting of prostate disease-specific changes for PAP, PSA and other secreted prostatic glycoproteins.

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Available from: Oliver John Semmes, Mar 18, 2014
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    • "Benign prostatic hyperplasia (BPH) has the highest prevalence among prostate diseases and, beside this, its etiology is also poorly understood [6]. Both diseases are usually associated with genetics, metabolic [5], proteomics [22] and glycomic alterations [28]. "
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    ABSTRACT: Prostatic Adenocarcinoma (PA) and Benign Prostatic Hyperplasia (BPH) have their etiology not fully understood mainly in glycidic aspects. Glycan changes are associated with cell alterations where glycosylation is carried out by glycosyltransferases, such as fucosyltransferases (FUTs). These enzymes catalyze the insertion of L-fucose residues in a variety of glycan structures often in the final stage of glycosylation. The present study aimed to investigate the expression of FUT3 and FUT6 in PA and BPH as well as to correlate immunostaining of these transferases with PA clinic-histopathologic data. The FUT3 and FUT6 expressions were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded biopsies of PA (n=40) and BPH (n=40). FUT3 and FUT6 showed a high expression in both prostatic diseases, especially FUT6. FUT6 was more immunoexpressed in PA cases than the FUT3 (p<0.0001) as well as in BPH cases but in a not significant way (p=0.0661). Besides, FUT3 was more expressed in BHP lesion than in PA cases (p<0.0001). Our study presented a new data about FUT3 and FUT6 expression in PA and BPH, revealing high FUT6 expression in both lesions and FUT3 overexpression in BHP in relation to PA, proposing that this enzyme could be a promising biomarker for benign prostate alterations.
    Preview · Article · Jun 2013 · Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry
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    • "The value of such studies may be supported by an interesting finding suggesting altered glycosylation of seminal gonadotropin subunits in subfertile men (Zenzmaier et al. 2011). Another promising, but still weakly studied glycoprotein is prostate acid phosphatase (White et al. 2009), with high-mannosetype glycans decreased and elevated multiantennary oligosaccharides in PC, but not in BPH. "
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    ABSTRACT: Context: Disturbed protein-carbohydrate interactions may underlie the molecular mechanism of some diseases of the male reproductive tract, including infertility and prostate diseases. Objective: To summarize the current knowledge on the glycosylation patterns of glycodelin-S, fibronectin, prostate-specific antigen, and α(1)-acid glycoprotein. Results: Some rare glycoepitopes have been found in seminal plasma glycoproteins: high-mannose and polylactosamine-type glycans, and N-glycans containing N-acetyl-galactosamine. The glycosylation profiles occur altered in pathological conditions. Conclusion: Further detailed studies may lead up to indicate the biomarkers useful in the management of male reproductive tract disorders.
    Full-text · Article · Oct 2012 · Biomarkers
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    • "The glycosylation of proteins is cell specific and the N-linked glycan a protein carries reflects modifications occurring in the cell from which it came [1]. Sugar (glycan) structures on the same protein secreted from malignant or diseased tissue and normal cells may, and often do, differ [2] [3] [4] [5] [6] [7]. Indeed, we and others, have observed changes in N-linked glycosylation with the development of cirrhosis and hepatocellular carcinoma (HCC) [8] [9] [10] [11] [12] [13] [14] [15] [16]. "
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    ABSTRACT: Changes in glycosylation have long been associated with disease. While there are many methods to detect changes in glycosylation, plant derived lectins are often used to determine changes on specific proteins or molecules of interest. One change in glycosylation that has been observed by us and by others is a disease or antigen associated increase in fucosylation on N-linked glycans. To measure this change, the fucose binding Aleuria aurantia lectin (AAL) is often utilized in plate and solution based assays. AAL is a mushroom derived lectin that contains five fucose binding sites that preferentially bind fucose linked (α-1,3, α-1,2, α-,4, and α-1,6) to N-acetyllactosamine related structures. Recently, several reports by us and by others have indicated that specific fucose linkages found on certain serum biomarker glycoprotein's are more associated with disease than others. Taking a site-directed mutagenesis approach, we have created a set of recombinant AAL proteins that display altered binding affinities to different analytes containing various fucose linkages.
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