Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cells play an important role in cancer immunosurveillance and tumor destruction. However, tumor cells alter immune responses by modulating immune cells through antigen stimulation and immunoregulatory cytokines. A better understanding of the interplay between tumor cells and T cells might provide new strategies to enhance antitumor immunity. Through an antigen-screening approach using colorectal tumor-reactive T cells, we identified an HLA-DR11-restricted T-cell epitope encoded by KIAA0040 as well as MHC-unrestricted human galectin-3 (Gal-3) expressed by tumor cells. Although the biological function of KIAA0040 remains to be determined, we found that Gal-3 functioned as an immune regulator for direct T-cell activation and function. T-cell activation induced by Gal-3 resulted in T-cell apoptosis. We showed that a high level of expression of Gal-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we showed that delivery of high doses of Gal-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8(+) T cells. These findings suggest that Gal-3 may function as an immune regulator to inhibit T-cell immune responses and promote tumor growth, thus providing a new mechanism for tumor immune tolerance.
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PMID:Tumor-associated galectin-3 modulates the function of tumor-reactive T cells. 1875 39

Galectin-3 (Gal-3) is a beta-galactoside-binding protein that is involved in cancer progression and metastasis. Using a progressive human melanoma tissue microarray, we previously demonstrated that melanocytes accumulate Gal-3 during the progression from benign to dysplastic nevi to melanoma and further to metastatic melanoma. Herein, we show that silencing of Gal-3 expression with small hairpin RNA results in a loss of tumorigenic and metastatic potential of melanoma cells. In vitro, Gal-3 silencing resulted in loss of tumor cell invasiveness and capacity to form tube-like structures on collagen ("vasculogenic mimicry"). cDNA microarray analysis after Gal-3 silencing revealed that Gal-3 regulates the expression of multiple genes, including endothelial cell markers that appear to be aberrantly expressed in highly aggressive melanoma cells, causing melanoma cell plasticity. These genes included vascular endothelial-cadherin, which plays a pivotal role in vasculogenic mimicry, as well as interleukin-8, fibronectin-1, endothelial differentiation sphingolipid G-protein receptor-1, and matrix metalloproteinase-2. Chromatin immunoprecipitation assays and promoter analyses revealed that Gal-3 silencing resulted in a decrease of vascular endothelial-cadherin and interleukin-8 promoter activities due to enhanced recruitment of transcription factor early growth response-1. Moreover, transient overexpression of early growth response-1 in C8161-c9 cells resulted in a loss of vascular endothelial-cadherin and interleukin-8 promoter activities and protein expression. Thus, Gal-3 plays an essential role during the acquisition of vasculogenic mimicry and angiogenic properties associated with melanoma progression.
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PMID:Expression profiling of Galectin-3-depleted melanoma cells reveals its major role in melanoma cell plasticity and vasculogenic mimicry. 1898 6

Galectin-3 (gal-3) is a glycoprotein involved in various physiological cellular processes. Altered expression/loss of function of gal-3 is suggested to be involved in the pathogenesis and further progression of various human cancer entities. The aim of the present investigation was to elucidate the role of galectin-3 in the development and/or progression of non-muscle invasive (pTa, pT1) transitional cell carcinoma (TCC) of the urinary bladder. Gal-3 was analyzed by immunohistochemistry in 162 randomly selected non-muscle invasive bladder cancer specimens (pTa, 91; pT1, 71) using tissue microarray technique. It was compared with various patient and tumour characteristics (t-test). In addition, the role of gal-3 in association with tumour recurrence and progression was investigated (Log-rank test, Cox regression analysis). Gal-3 was found to be negatively correlated with tumour grade (p<0.02). Within the group of non-muscle invasive TCC, gal-3 could not differentiate between pTa and pT1 tumours (p=0.50), and within the subgroup of pTa tumours, loss of gal-3 determined the likelihood for the development of recurrent disease (p<0.03; Student's t-test). Furthermore, as demonstrated by Kaplan-Meier analysis, the expression level of gal-3 was identified to predict the duration of recurrence-free survival (p=0.01). In the multivariate analysis, gal-3 was found as an independent prognostic marker for predicting recurrence among the cohort of bladder tumours classified as pTa. In conclusion, loss of galectin-3 appears to be involved in the carcinogenesis of TCC and to serve as a valuable biological variable to identify a subgroup of Ta bladder cancer patients at high risk for the development of recurrent disease.
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PMID:Decreased expression of galectin-3 predicts tumour recurrence in pTa bladder cancer. 1902 Jul 21

The aim of the study is to characterize the expression pattern of galectin-3 (Gal-3) in renal tissues of patients with systemic lupus erythematosus (SLE) nephritis and to determine whether tissue and serum Gal-3 are associated with SLE nephritis. Gal-3 expressions were examined with immunohistochemistry in renal biopsy specimens of 88 patients with SLE nephritis and in five normal specimens. Activity and chronicity indexes and glomerular Gal-3 expressions were analysed in each specimen. Serum Gal-3 levels were measured using enzyme-linked immunosorbent assays in 20 patients with SLE, including 11 with nephritis, and in 50 healthy controls. Glomerular Gal-3 expression was observed in 81.8% (72/88) of patients with SLE nephritis but not in 5 controls. Gal-3 staining was attributed mainly to its cellular expression rather than its deposition, and Gal-3 expression levels were correlated with histologic activity indexes, anti-dsDNA titers, and complement 3 and 4 levels. Serum Gal-3 levels were higher in patients with SLE, particularly in those with nephritis, than in healthy controls, and correlated with anti-dsDNA titers. In conclusion, glomerular Gal-3 expression in renal tissue and serum Gal-3 levels were elevated in patients with SLE nephritis versus healthy controls; moreover, they reflected disease activity. These findings suggest that Gal-3 might contribute to the inflammatory process in SLE.
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PMID:Renal expression of galectin-3 in systemic lupus erythematosus patients with nephritis. 1907 65

This study aimed at determining the contribution of intestinal bifidobacteria to the immune system activation using widely distributed galectins as markers of immune cell homoeostasis. In human flora-associated mice, bacteria were enumerated in the gut, blood, spleen, liver and lungs, while the expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) was estimated by PCR in the intestine and real-time quantitative PCR in the other organs. Gal-1 and -3 were rarely expressed in the intestine. In blood, only Gal-1 was expressed while both galectins were expressed in all other organs. A high prevalence of colonic bifidobacteria was associated with a lower expression of both pulmonary galectins, whose levels negatively correlated with bifidobacterial counts. Caecal bifidobacterial counts also negatively correlated with pulmonary Gal-3 mRNA levels. The spleen was the only organ showing an upregulation of Gal-1 expression related to its bacterial contamination. However, this upregulation was only observed when bifidobacteria were not detected in the colon. A putative mechanism explaining the reduced expression of galectins when bifidobacteria highly colonize the mouse intestine could be that, by reducing the bacterial translocation, bifidobacteria also lead to a decreased blood concentration of substances produced by intestinal bacteria.
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PMID:Intestinal colonization with bifidobacteria affects the expression of galectins in extraintestinal organs. 1907 20

Galectin-3 (Gal-3) is secreted by activated macrophages. In hypertension, Gal-3 is a marker for hypertrophic hearts prone to develop heart failure. Gal-3 infused in pericardial sac leads to cardiac inflammation, remodeling, and dysfunction. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a naturally occurring tetrapeptide, prevents and reverses inflammation and collagen deposition in the heart in hypertension and heart failure postmyocardial infarction. In the present study, we hypothesize that Ac-SDKP prevents Gal-3-induced cardiac inflammation, remodeling, and dysfunction, and these effects are mediated by the transforming growth factor (TGF)-beta/Smad3 signaling pathway. Adult male rats were divided into four groups and received the following intrapericardial infusion for 4 wk: 1) vehicle (saline, n = 8); 2) Ac-SDKP (800 microg x kg(-1) x day(-1), n = 8); 3) Gal-3 (12 microg/day, n = 7); and 4) Ac-SDKP + Gal-3 (n = 7). Left ventricular ejection fraction, cardiac output, and transmitral velocity were measured by echocardiography; inflammatory cell infiltration, cardiomyocyte hypertrophy, and collagen deposition in the heart by histological and immunohistochemical staining; and TGF-beta expression and Smad3 phosphorylation by Western blot. We found that, in the left ventricle, Gal-3 1) enhanced macrophage and mast cell infiltration, increased cardiac interstitial and perivascular fibrosis, and causes cardiac hypertrophy; 2) increased TGF-beta expression and Smad3 phosphorylation; and 3) decreased negative change in pressure over time response to isoproterenol challenge, ratio of early left ventricular filling phase to atrial contraction phase, and left ventricular ejection fraction. Ac-SDKP partially or completely prevented these effects. We conclude that Ac-SDKP prevents Gal-3-induced cardiac inflammation, fibrosis, hypertrophy, and dysfunction, possibly via inhibition of the TGF-beta/Smad3 signaling pathway.
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PMID:N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. 1909 14

A subset of patients with papillary thyroid cancer (PTC) present with aggressive disease that is refractory to conventional treatment. Novel therapies are needed to treat this group of patients. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with anti-apoptotic activity. Over 30 studies in the last 3 years have reported that Gal-3 is highly expressed in PTC relative to normal thyrocytes. In this study, we show that Gal-3 silencing with RNA interference stimulates apoptosis, while Gal-3 overexpression protects against both TRAIL- and doxorubicin-induced apoptosis in PTC cells. The anti-apoptotic activity and chemoresistance related to Gal-3 function can be partially reversed through the inhibition of the PI3K-Akt pathway, suggesting that Gal-3 acts, at least in part, on the PI3K-Akt axis. These observations support further evaluation of Gal-3 as a potential therapeutic target in patients with aggressive PTC.
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PMID:Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells. 1912 5

Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectin family and plays an important role in inflammation. However, the precise role of Gal-3 in autoimmune diseases remains obscure. We have investigated the functional role of Gal-3 in experimental autoimmune encephalomyelitis (EAE) following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Gal-3 deficient (Gal-3-/-) mice developed significantly milder EAE and markedly reduced leukocyte infiltration in the CNS compared with similarly treated wild-type (WT) mice. Gal-3-/- mice also contained fewer monocytes and macrophages but more apoptotic cells in the CNS than did WT mice. Following Ag stimulation in vitro, lymph node cells from the immunized Gal-3-/- mice produced less IL-17 and IFN-gamma than did those of the WT mice. In contrast, Gal-3-/- mice produced more serum IL-10, IL-5, and IL-13 and contained higher frequency of Foxp3+ regulatory T cells in the CNS than did the WT mice. Furthermore, bone marrow-derived dendritic cells from Gal-3-/- mice produced more IL-10 in response to LPS or bacterial lipoprotein than did WT marrow-derived dendritic cells. Moreover, Gal-3-/- dendritic cells induced Ag-specific T cells to produce more IL-10, IL-5, and IL-12, but less IL-17, than did WT dendritic cells. Taken together, our data demonstrate that Gal-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10 production.
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PMID:Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. 1912 60

Galectin-1 (Gal-1) and galectin-3 (Gal-3) are widely expressed galectins with immunoregulatory functions in animals. To explore their glycan specificity, we developed microarrays of naturally occurring glycans using a bifunctional fluorescent linker, 2-amino-N-(2-aminoethyl)-benzamide (AEAB), directly conjugated through its arylamine group by reductive amination to free glycans to form glycan-AEABs (GAEABs). Glycans from natural sources were used to prepare over 200 GAEABs, which were purified by multidimensional high-pressure liquid chromatography and covalently immobilized onto N-hydroxysuccinimide-activated glass slides via their free alkylamine. Fluorescence-based screening demonstrated that Gal-1 recognizes a wide variety of complex N-glycans, whereas Gal-3 primarily recognizes poly-N-acetyllactosamine-containing glycans independent of N-glycan presentation. GAEABs provide a general solution to glycan microarray preparation from natural sources for defining the specificity of glycan-binding proteins.
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PMID:Novel fluorescent glycan microarray strategy reveals ligands for galectins. 1917 4

Galectin-3 (Gal-3) is an anti-apoptotic molecule of the beta-galactoside-binding lectin family. Gal-3 is down-regulated by wt-p53 and this repression is required for p53-induced apoptosis. Since poorly differentiated thyroid carcinomas (PDTCs) and anaplastic thyroid carcinomas (ATCs) frequently harbour p53 mutations, we asked whether Gal-3 expression and activity could be influenced by such mutations in these tumours. We found a positive correlation between Gal-3 expression and p53 mutation in human thyroids and in thyroid carcinoma cell lines (TCCLs) harbouring different p53 mutations. Gal-3 was over-expressed in most ATCs and TCCLs, especially those with the most frequently detected p53 mutation (p53(R273H)). Over-expression of p53(R273H) in two p53-null cells (SAOS-2 and SW-1736) as well as in two wt-p53-carrying TCCLs (TPC-1 and K1), stimulated Gal-3 expression, while interference with p53(R273H) endogenous expression in ARO cells down-regulated Gal-3 expression. Conversely, over-expression of wt-p53 in ARO cells restored the inhibitory effect on Gal-3 expression. ARO cells are highly resistant to apoptosis and express both p53 and Gal-3, which are increased upon cisplatin treatment. Interference with Gal-3 expression in these cells stimulated their chemosensitivity. In conclusion, gain-of-function p53 mutant acquires the de novo ability to stimulate Gal-3 expression and to increase chemoresistance in ATCs.
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PMID:Gal-3 is stimulated by gain-of-function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas. 1919 18


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