Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have identified a subclone cell line (PC-J) which was isolated from a metastatic human prostate cell line, PC-3. In vitro matrigel invasion assays and xenograft animal studies suggested that matriptase was a putative metastatic gene in human prostate carcinoma cells. Although low metastatic prostate tumor cells, LNCaP, also expressed high levels of matriptase mRNA, gelatin zymography indicated that LNCaP cells had extremely low matriptase activity. Further studies using RT-PCR and lectin blotting assays revealed that the expression of N-acetylglucosaminyltransferase V (MGAT5), a glycoprotein that stabilizes matriptase, was low in LNCaP cells compared to PC-3 and PC-J cells. The transient overexpression of MGAT5 significantly enhanced the activity of matriptase and the invasion ability in the LNCaP cells. Knock-down of MGAT5 in PC-3 cells attenuated the metastatic ability of the cells, as determined by the in vitro invasion assay and the xenograft animal studies. Matriptase and MGAT5 may play important role in the metastasis of prostate cancer.
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PMID:Evaluating the function of matriptase and N-acetylglucosaminyltransferase V in prostate cancer metastasis. 1864 38

Aberrant N-linked glycans promote the malignant potential of cells by enhancing the epithelial-to-mesenchymal transition and the invasive phenotype. To identify small molecule inhibitors of N-glycan biosynthesis, we developed a chemical screen based on the ability of the tetravalent plant lectin L-phytohemagglutinin (L-PHA) to bind and crosslink surface glycoproteins with beta1,6GlcNAc-branched complex type N-glycans and thereby induce agglutination and cell death. In this screen, Jurkat cells were treated with a library of off-patent chemicals (n = 1,280) to identify molecules that blocked L-PHA-induced death. The most potent hit from this screen was the cardiac glycoside (CG) dihydroouabain. In secondary assays, a panel of CGs was tested for their effects on L-PHA-induced agglutination and cell death. All of the CGs tested inhibited L-PHA-induced death in Jurkat cells, and the most potent CG tested was digoxin with an EC(50) of 60 +/- 20 nmol/L. Digoxin also increased the fraction of some concanavalin A-binding N-glycans. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, digoxin specifically increased GlcNAc(1)Man(3)GlcNAc(2)Fuc(1) and GlcNAc(2)Man(3)GlcNAc(2)Fuc(1) oligosaccharides demonstrating an impairment of the N-glycan pathway. Consistent with this effect on the N-glycan pathway, digoxin inhibited N-glycosylation-mediated processes of tumor cell migration and invasion. Furthermore, digoxin prevented distant tumor formation in two mouse models of metastatic prostate cancer. Thus, taken together, our high throughput screen identified CGs as modifiers of the N-glycan pathway. These molecules can be used as tools to better understand the role of N-glycans in normal and malignant cells. Moreover, these results may partly explain the anticancer effect of CGs in cardiovascular patients.
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PMID:Inhibition of the sodium/potassium ATPase impairs N-glycan expression and function. 1870 93

Fibronectin (FN) is a multifunctional glycoprotein involved in cell-matrix interactions. It exhibits a complex pattern of forms differing in respect to aminoacid and oligosaccharide composition. In this study we examined glycobiochemical and functional properties of the FN in benign prostatic hyperplasia (BPH) and prostatic cancer (PCa), attempting to resolve disease-related differences. Two BPH sera pools and three PCa sera pools were used as the FN source. The affinity-purified molecule was characterized by SDS-PAGE, immuno- and lectin blot, lectin-affinity chromatography and adhesion assay. BPH FN existed as intact molecule, giving the main immunoreactive band at 220 kDa. In contrast, PCa FN comprised three main immunoreactive fragments of 140, 110 and 90 kDa. As for glycosylation the ratio of altogether lectin-reactive PCa FN was different from that of BPH FN manifested as a decrease of Con A- and an increase of LCA-reactive moieties. Fibroblasts adhered to both FN preparations in a concentration dependent manner, but with a significantly lower efficiency to PCa FN. The results obtained showing distinct structural characteristics of PCa FN compared to BPH FN could be important for modulation of its ligand and recognition properties expressed as gain or loss of functions or as specific markers of its origin.
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PMID:Fibronectin pattern in benign hyperplasia and cancer of the prostate. 1877 91

Currently, serum prostate-specific antigen (PSA) is used for the early detection of prostate cancer despite its low specificity in the range of 4-10 ng/mL. Because aberrant glycosylation is a fundamental characteristic of tumor genesis, the objective of this study was to investigate whether changes in PSA glycosylation may be used to improve the cancer specificity of PSA. We developed five lectin immunosorbant assays to analyze the glycosylation patterns of PSA in serum. Each assay sandwiches serum PSA between a PSA monoclonal antibody and a biotinylated lectin and then tags the biotin complex using a streptavidin SULFO TAG for electrochemiluminescence detection. Low limits of detection (0.04-1.35 ng/mL), good reproducibility (%CVs < 10%), and direct analysis of PSA glycosylation in sera suggest these assays may have a potential role in improving PSA's cancer specificity. Clinical performance was evaluated in 52 human subjects (26 cancer and 26 noncancer). ROC analysis showed that the total SNA assay (AUC = 0.71) appeared to perform better than percent free PSA (AUC = 0.54) in its diagnostic gray zone between 10 and 20% in a subset of 21 subjects. A separate study of 16 additional subjects showed similar findings.
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PMID:Glycoproteomics for prostate cancer detection: changes in serum PSA glycosylation patterns. 1903 87

The present investigation was a lectin-based diagnosis of malignant prostate cancer (PC) by the interaction of phytohemagglutinin (PHA lectin) from Phaseolus vulgaris with the glycan part of serum prostate specific antigen (PSA) of patients with prostatic disorder. This was confirmed by the interaction between PHA and purified PSA obtained from serum by electrophoretic separation and finally by HPLC chromatography. The precipitate of carbohydrate content after binding of PHA with purified PSA of PC was significantly higher than that of benign prostate hyperplasia (BPH) and/or normal serum PSA. The results suggest that there may be a striking difference in glycosylation pattern of PSA between BPH and PC. The cut off value > or = 10 microg/ml of the carbohydrate content of PHA-PSA precipitate indicates strong suspicion for PC irrespective of total serum PSA cut off level > or = 4.0 ng/ml by conventional immunoassay method and this may be taken as a guideline in differentiating PC and BPH. Key words: prostate cancer, BPH, PSA, lectin.
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PMID:Clinical utility of the interaction between lectin and serum prostate specific antigen in prostate cancer. 1915 48

Galectin-3 is a beta-galactoside-binding protein involved in immunomodulation, cell interactions, cancer progression, and pathogenesis of infectious organisms. We report the identification and characterization of galectin-3 in human semen. In the male reproductive tract, the approximately 30 kDa galectin-3 protein was identified in testis, epididymis, vas deferens, prostate, seminal vesicle, and sperm protein extracts. In seminal plasma, galectin-3 was identified in the soluble fraction and in prostasomes, cholesterol-rich, membranous vesicles that are secreted by the prostate and incorporated into seminal plasma during ejaculation. Two-dimensional immunoblot analysis of purified prostasomes identified five galectin-3 isoelectric variants with a pI range of 7.0 to 9.2. Affinity purification and tandem mass spectrometry of beta-galactoside-binding proteins from prostasomes confirmed the presence of galectin-3 in prostasomes and identified a truncated galectin-3 variant. The intact galectin-3 molecule contains a carbohydrate recognition domain and a non-lectin domain that interacts with protein and lipid moieties. The identification of a monovalent galectin-3 fragment with conserved carbohydrate-binding activity indicates the functional relevance of this truncation and suggests a regulatory mechanism for galectin-3 in prostasomes. Surface biotinylation studies suggested that galectin-3 and the truncated galectin-3 variant are localized to the prostasome surface. Prostasomes are proposed to function in immunosuppression and regulation of sperm function in the female reproductive tract, are implicated in facilitating sexually-transmitted infections, and are indicated in prostate cancer progression. Given the overlap in functional significance, the identification of galectin-3 in prostasomes lays the groundwork for future studies of galectin-3 and prostasomes in reproduction, disease transmission, and cancer progression.
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PMID:Galectin-3 is associated with prostasomes in human semen. 1983 May 50

N-glycosylation status of purified beta-haptoglobin separated from sera of patients with prostate cancer was studied in comparison to that of sera from patients with benign prostate diseases, or normal subjects. Two different approaches, as summarized below, one based on binding of lectins and antibodies to beta-haptoglobin, the other on mass spectrometry of released N-linked glycans from beta-haptoglobin, were performed. Some of the results were useful for distinction of prostate cancer vs. benign prostate diseases. i) Binding of Phaseolus vulgaris-L lectin (PHA-L), defining the GlcNAcbeta6Manalpha6Man side chain present in tri- or tetra-antennary N-linked glycans, to beta-haptoglobin was higher for cases of prostate cancer and high-grade prostate intraepithelial neoplasia than for benign diseases. Binding of Aleuria aurantia lectin (AAL) defining Fucalpha3-, alpha4-, or alpha6-GlcNAc, or monoclonal antibody directed to sialyl-Le(x), to beta-haptoglobin was also higher for some of the cancer cases than for benign diseases. Many other lectins and antibodies showed no binding to beta-haptoglobin, or showed no significant difference between cancer vs. benign diseases. ii) Mass spectrometric analysis of N-linked glycans of beta-haptoglobin released by Peptide N-glycosidase-F showed enhanced expression of monosialyl tri-antennary structures in prostate cancer cases. Thus, binding of PHA-L to affinity-purified beta-haptoglobin from sera of patients could lead to development of useful tools for differential diagnosis of prostate cancer vs. benign prostate diseases.
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PMID:N-glycosylation status of beta-haptoglobin in sera of patients with prostate cancer vs. benign prostate diseases. 1995 48

A prostate-specific antigen (PSA) is widely used as a diagnostic marker for prostate cancer (PC) because of its high specificity. However, elevated serum PSA does not occur only in PC but also in benign prostatic hyperplasia (BPH). Since the structural changes of N-glycans during carcinogenesis are common phenomena, we investigated whether PC-specific N-glycans are linked to PSA. We first analyzed the carbohydrate structures of PSA derived from seminal fluid, serum of BPH and PC patients, and PC cell line, namely, LNCaP using eight lectin-immobilized columns and then with enzyme-linked immunosorbent assay (ELISA). The fraction of serum PSA from PC patients bound to both Fucalpha1-2Gal and betaGalNAc binding Trichosanthes japonica agglutinin-II (TJA-II) column, while that from BPH patients did not exhibit this binding ability, thereby implying that there is elevated expression of alpha1,2-fucosylation and beta-N-acetylgalactosaminylation of PSA during carcinogenesis. We then performed a real-time polymerase chain reaction (PCR) and confirmed that these structural changes were responsible for the elevated expression of fucosyltransferase I (FUT1) and beta-N-acetylgalactosaminyltransferase 4(B4GALNT4). Second, we measured TJA-II-bound PSA contents and the binding ratios of TJA-II column chromatography in serum PSA samples from 40 patients of both PC and BPH. The results indicated that both TJA-II-bound PSA content and TJA-II binding ratios (%) could be used to discriminate between PC and BPH with more than 95% probability, and TJA-II-bound PSA can be regarded as a potential marker of PC.
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PMID:alpha1,2-Fucosylated and beta-N-acetylgalactosaminylated prostate-specific antigen as an efficient marker of prostatic cancer. 2000 18

The accuracy in quantitative analysis of N-linked glycopeptides and glycosylation site mapping in cancer is critical to the fundamental question of whether the aberration is due to changes in the total concentration of glycoproteins or variations in the type of glycosylation of proteins. Toward this goal, we developed a lectin-directed tandem labeling (LTL) quantitative proteomics strategy in which we enriched sialylated glycopeptides by SNA, labeled them at the N-terminus by acetic anhydride ((1)H(6)/(2)D(6)) reagents, enzymatically deglycosylated the differentially labeled peptides in the presence of heavy water (H(2)(18)O), and performed LC/MS/MS analysis to identify glycopeptides. We successfully used fetuin as a model protein to test the feasibility of this LTL strategy not only to find true positive glycosylation sites but also to obtain accurate quantitative results on the glycosylation changes. Further, we implemented this method to investigate the sialylation changes in prostate cancer serum samples as compared to healthy controls. Herein, we report a total of 45 sialylated glycopeptides and an increase of sialylation in most of the glycoproteins identified in prostate cancer serum samples. Further quantitation of nonglycosylated peptides revealed that sialylation is increased in most of the glycoproteins, whereas the protein concentrations remain unchanged. Thus, LTL quantitative technique is potentially an useful method for obtaining simultaneous unambiguous identification and reliable quantification of N-linked glycopeptides.
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PMID:Investigation of sialylation aberration in N-linked glycopeptides by lectin and tandem labeling (LTL) quantitative proteomics. 2092 42

Death from prostate cancer is most frequently a result of metastatic disease. A key step in the process of metastasis is the attachment of circulatory tumor cells to target organ endothelium. This process is thought to be mediated by lectins, a class of cell surface proteins that bind two or more carbohydrate groups. Using fluorescent microscopy and fluorescein isothiocyanate (FITC) conjugated lectins, the presence of various carbohydrates was examined in the following tumorigenic and non-tumorigenic cell lines: rat prostate epithelial (EPYP-2, EPYP-1), rat prostate endothelial (YPEN-2, YPEN-1, YPEN-2PV), Dunning rat prostate cancer cell lines (MLL, ML, AT6.3, AT.1, AT2.1, GP9F3), and three tumorigenic human prostate cell lines (LNCaP, PC3, PC3 bone). The lectin Triticum vulgaris (WGA) was found to readily bind the carbohydrates N-acetylglucosamine and sialic acid on the plasma membrane of tumorigenic cell lines. Interestingly, WGA bound carbohydrates located to the nucleus and cytoplasm in non-tumorigenic cell lines, indicating that N-acetylglucosamine and sialic acid residues are preferentially expressed on the cell membrane of prostate cancer cells. Lectin staining patterns in cell lines of varying metastatic potential revealed no significant difference between highly metastatic vs. low metastatic cell lines. Observations revealed an absence of N-acetylgalactosamine and L-fucose in all rat Dunning, epithelial and endothelial cell lines as well as all human prostate cancer cell lines except for the androgen insensitive human prostate cancer cell line PC3, in which L-fucose residues were detected in the nucleus and on the plasma membrane. PC3 bone cells, which metastasized selectively to bone, demonstrated the presence of galactose residues whereas PC3 cells did not, suggesting that preference for target organ endothelium may be influenced by the expression of carbohydrate residues. These data indicate that differential carbohydrate expression may play an important role in prostate cancer biology.
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PMID:Differential carbohydrate expression in tumorigenic vs nontumorigenic prostate cell-lines. 2155 71


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