UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galectin 3 (Gal-3), a member of the beta-galactoside binding lectin family, exhibits antiapoptotic functions, and its aberrant expression is involved in various aspects of tumor progression. Here we show that p53-induced apoptosis is associated with transcriptional repression of Gal-3. Previously, it has been reported that phosphorylation of p53 at Ser46 is important for transcription of proapoptotic genes and induction of apoptosis and that homeodomain-interacting protein kinase 2 (HIPK2) is specifically involved in these functions. We show that HIPK2 cooperates with p53 in Gal-3 repression and that this cooperation requires HIPK2 kinase activity. Gene-specific RNA interference demonstrates that HIPK2 is essential for repression of Gal-3 upon induction of p53-dependent apoptosis. Furthermore, expression of a nonrepressible Gal-3 prevents HIPK2- and p53-induced apoptosis. These results reveal a new apoptotic pathway induced by HIPK2-activated p53 and requiring repression of the antiapoptotic factor Gal-3.
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PMID:Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis. 1673 36

Increased serum haptoglobin concentration and changes in its glycosylation have been reported in certain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. In this study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp) and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases (CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurement of serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitative analysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by using lectin affinity purification and 2D gel electrophoresis and investigation of their relationships with tumor stage. The concentrations of serum Hp in HCC patients were significantly higher than those in noncancer patients with CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR) model was developed from the training data set and used to classify the validation cases. At a specificity of 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests that purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in the HCC patients. Serum concentrations of these glycoproteins were significantly higher in the patients with advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is a potential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improve the diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation is specific to HCC and associated tumor progression.
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PMID:Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: a glycoproteomic approach. 1702 40

beta-Galactoside alpha2,6-sialyltransferase (ST6Gal.I) is the principal sialyltransferase responsible for the biosynthesis of the sialyl alpha2,6-galactosyl linkage. This enzyme and its cognate glycosidic structure are overexpressed in several malignancies and are related to cancer progression. The expression of the enzyme is regulated primarily through the expression of three principal mRNA species differing in the 5'-untranslated exons. The form known as YZ is considered associated with the basal expression of the gene, while forms H and X are specific to the liver and B-lymphocytes, respectively. The authors have studied the expression of ST6Gal.I activity by two different methods using a panel of human cancer cell lines: the expression of alpha2,6-sialylated sugar chains by the lectin from Sambucus nigra (SNA), and the expression of the different mRNA species by RT-PCR using oligonucleotide primers complementary to the isoform-specific regions. Very high levels of ST6Gal.I activity result in high levels of SNA reactivity and are associated with the expression of the H transcript in colon and liver cell lines, and of the X transcript in B cells.
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PMID:Beta-galactoside alpha2,6-sialyltransferase and the sialyl alpha2,6-galactosyl-linkage in tissues and cell lines. 1707 10

The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins normally contain high amounts of O-linked carbohydrate structures that may influence immune reactions to this antigen. During malignant transformation, certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their sialylated forms become exposed. The role of these glycan structures in tumor biology is unknown, but their presence is known to correlate with poor prognosis in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn-antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate recognition and uptake molecules on dendritic cells (DC). We identified the macrophage galactose type C-type lectin (MGL), expressed by both DC and macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1 was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA), which is associated with poor prognosis in colorectal cancer. The detection of MGL positive cells in situ at the tumor site together with the modified glycosylation status of MUC1 to target MGL on DC suggests that MGL positive antigen presenting cells may play a role in tumor progression.
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PMID:The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma. 1719 76

Tumor-associated macrophages (TAMs) have a complex and ambivalent relationship with tumor progression and elimination. Though TAMs are reported to have pro- and anti-tumor roles, upon modification and activation TAMs can develop tumoricidal activities and thus might have applications in cancer therapy. Various immunomodulatory compounds could be used to modulate TAMs. In this study we used Abrus agglutinin, a plant lectin, in its native and heat-denatured forms, to investigate its effect on TAMs in Dalton's lymphoma-bearing mice. We found that treatment with both native (NA) and heat-denatured agglutinin (HDA) activated the TAMs, which showed significantly increased in vitro cytotoxicity towards tumor cells and production of nitric oxide but no difference in TNF-alpha production. The tumoricidal activities of both NA and HDA were dependent upon the activation of TAMs as in macrophage-depleted Dalton's lymphoma-bearing mice NA and HDA treatment could not decrease the number of tumor cells significantly. Thus, NA and HDA could be used as modulators of TAMs, for their therapeutic use in cancer.
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PMID:Effects of native and heat-denatured Abrus agglutinin on tumor-associated macrophages in Dalton's lymphoma mice. 1786 44

Microvessel density is a frequently used parameter of angiogenesis, which is a complex multistep process necessary for tumor progression. The aim of this study was to compare the microvessel density of normal lymph node biopsies with those diagnosed with lymphoma in dogs. Furthermore, we sought to determine if there was any correlation between microvessel density and vascular endothelial growth factor expression in canine lymphoma, representing a potential target for anti-angiogenic therapy. Combined immunohistochemistry (von Willebrand factor) and lectin histochemistry was used to highlight microvessels in 40 untreated canine lymphomas and 14 normal lymph nodes. To evaluate microvessel density, the number of profiles of blood vessels per unit area was calculated. Fifty image fields (a total area of 5.68 mm(2)) were sampled for each specimen in a systematic random, way. We found a significant difference between the microvessel densities (MVD) of normal and neoplastic lymph nodes (177+/-35 versus 241+/-72 microvessel profiles/mm(2)). Classifying lymphoma samples according to the working formulation and the Kiel classification system revealed no significant differences in MVD between different grade malignancies. Immunohistochemical demonstration of the proangiogenic protein vascular endothelial growth factor showed expression in 60% of canine lymphomas, although there was no correlation between microvessel density and vascular endothelial growth factor expression. As an increase in tumor angiogenesis was observed in lymphoma samples compared to normal canine lymph node tissue, additional anti-angiogenic therapy, besides conventional chemotherapy as a lymphoma treatment may be effective. The optimal target among many pro-angiogenic factors has yet to be elucidated.
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PMID:Microvessel density in normal lymph nodes and lymphomas of dogs and their correlation with vascular endothelial growth factor expression. 1788 71

Supramolecular chemistry has been employed to develop flexible and adaptable multivalent neoglycoconjugates for binding galectin-1 (Gal-1). Gal-1, a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Self-assembled pseudopolyrotaxanes consisting of lactoside-displaying cyclodextrin (LCD) "beads" threaded onto polyviologen "strings" display mobile ligands as a result of cyclodextrin rotation about, and limited translation along, the polymer chain. The pseudopolyrotaxanes rapidly and efficiently precipitate Gal-1 and provide valency-corrected enhancements of up to 30-fold compared to native lactose and 20-fold over free LCD in a T-cell agglutination assay. A supramolecular statistical effect was observed, wherein the efficacy of Gal-1 inhibition correlates with the number of ligands connected to each other solely through mechanical and noncovalent interactions. Such flexible and adaptable self-assembled pseudopolyrotaxanes show promise for the study of multivalent interactions and targeting of therapeutically relevant lectins.
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PMID:Multivalent interactions between lectins and supramolecular complexes: Galectin-1 and self-assembled pseudopolyrotaxanes. 1796 21

Galectin-3 is a soluble endogenous lectin in vertebrates and is implicated in a variety of biological functions, including tumor cell adhesion, proliferation, differentiation, apoptosis, cancer progression and metastasis. In the present study, we analyzed the role of galectin-3 in apoptosis in human malignant lymphoma. Galectin-3 induced cell death in the HBL-2 human diffuse large B cell lymphoma cell line. A morphological examination and annexin V assays revealed that galectin-3-induced cell death is consistent with apoptosis and swainsonine, a potent inhibitor of alpha-mannosidase II, which catalyzes the synthesis of complex type N-linked oligosaccharides, inhibited galectin-3-induced apoptosis in HBL-2 cells. These results suggest that galectin-3 induces apoptosis in HBL-2 cells by interacting with cell surface N-linked oligosaccharides. Furthermore, treatment of cells with Vibrio Cholerae neuraminidase enhanced galectin-3-induced apoptosis, suggesting that cell surface sialylation regulates galectin-3-induced apoptosis in human B cell lymphoma. In conclusion, our results indicate that galectin-3-induced apoptosis is regulated by cell surface expression of N-glycans and sialic acid in human diffuse large B cell lymphoma. This mechanism may be involved in the malignant behavior of human lymphoma cells.
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PMID:Cell surface N-glycosylation and sialylation regulate galectin-3-induced apoptosis in human diffuse large B cell lymphoma. 1828 10

Colorectal cancer (CRC) remains a major worldwide cause of cancer-related morbidity and mortality largely due to the insidious onset of the disease. The current clinical procedures utilized for disease diagnosis are invasive, unpleasant, and inconvenient; hence, the need for simple blood tests that could be used for the early detection of CRC. In this work, we have developed methods for glycoproteomics analysis to identify plasma markers with utility to assist in the detection of colorectal cancer (CRC). Following immunodepletion of the most abundant plasma proteins, the plasma N -linked glycoproteins were enriched using lectin affinity chromatography and subsequently further separated by nonporous silica reversed-phase (NPS-RP)-HPLC. Individual RP-HPLC fractions were printed on nitrocellulose coated slides which were then probed with lectins to determine glycan patterns in plasma samples from 9 normal, 5 adenoma, and 6 colorectal cancer patients. Statistical tools, including principal component analysis, hierarchical clustering, and Z-statistics analysis, were employed to identify distinctive glycosylation patterns. Patients diagnosed with colorectal cancer or adenomas were shown to have dramatically higher levels of sialylation and fucosylation as compared to normal controls. Plasma glycoproteins with aberrant glycosylation were identified by nano-LC-MS/MS, while a lectin blotting methodology was used to validate proteins with significantly altered glycosylation as a function of cancer progression. The potential markers identified in this study for diagnosis to distinguish colorectal cancer from adenoma and normal include elevated sialylation and fucosylation in complement C3, histidine-rich glycoprotein, and kininogen-1. These potential markers of colorectal cancer were subsequently validated by lectin blotting in an independent set of plasma samples obtained from 10 CRC patients, 10 patients with adenomas, and 10 normal subjects. These results demonstrate the utility of this strategy for the identification of N -linked glycan patterns as potential markers of CRC in human plasma, and may have the utility to distinguish different disease states.
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PMID:Plasma glycoprotein profiling for colorectal cancer biomarker identification by lectin glycoarray and lectin blot. 1831 4

Growing insights into the functionality of lectin-carbohydrate interactions are identifying attractive new targets for drug design. As glycan recognition is regulated by the structure of the sugar epitope and also by topological aspects of its presentation, a suitable arrangement of ligands in synthetic glycoclusters has the potential to enhance their avidity and selectivity. If adequately realized, such compounds might find medical applications. This is why we focused on lectins of clinical interest, acting either as a potent biohazard (a toxin from Viscum album L. akin to ricin) or as a factor in tumor progression (human galectins-1, -3, and -4). Using a set of 14 calix[n]arenes (n=4, 6, and 8) with thiourea-linked galactose or lactose moieties, we first ascertained the lectin-binding properties of the derivatized sugar head groups conjugated to the synthetic macrocycles. Despite their high degree of flexibility, the calix[6,8]arenes proved especially effective for the plant AB-toxin, in the solid-phase model system with a single glycoprotein (asialofetuin) and with human tumor cells in vitro. The bioactivity of the calix[n]arenes was also proven for human galectins. Notably, selectivity for the tested tandem-repeat-type galectin-4 among the three subgroups was determined at the level of solid-phase and cell assays, the large flexible macrocycles again figuring prominently as inhibitors. Alternate and cone versions of calix[4]arene with lactose units distinguished between galectins-1 and -4 versus galectin-3 in cell assays. The results thus revealed bioactivity of galactose-/lactose-presenting calix[n]arenes for medically relevant lectins and selectivity within the family of adhesion/growth-regulatory human galectins.
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PMID:Calix[n]arene-based glycoclusters: bioactivity of thiourea-linked galactose/lactose moieties as inhibitors of binding of medically relevant lectins to a glycoprotein and cell-surface glycoconjugates and selectivity among human adhesion/growth-regulatory galectins. 1850 38

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