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Joane K Rustiguel, Ricardo O S Soares, Steve P Meisburger, Katherine M Davis, Kristina L Malzbender, Nozomi Ando, Marcelo Dias-Baruffi, Maria Cristina Nonato
Galectins are proteins involved in diverse cellular contexts due to their capacity to decipher and respond to the information encoded by β-galactoside sugars. In particular, human galectin-4, normally expressed in the healthy gastrointestinal tract, displays differential expression in cancerous tissues and is considered a potential drug target for liver and lung cancer. Galectin-4 is a tandem-repeat galectin characterized by two carbohydrate recognition domains connected by a linker-peptide. Despite their relevance to cell function and pathogenesis, structural characterization of full-length tandem-repeat galectins has remained elusive...
2016: Scientific Reports
Junko Nio-Kobayashi
Fifteen galectins, β-galactose-binding animal lectins, are known to be distributed throughout the body. We herein summarize current knowledge on the tissue- and cell-specific localization of galectins and their potential functions in health and disease. Galectin-3 is widely distributed in epithelia, including the simple columnar epithelium in the gut, stratified squamous epithelium in the gut and skin, and transitional epithelium and several regions in nephrons in the urinary tract. Galectin-2 and galectin-4/6 are gut-specific, while galectin-7 is found in the stratified squamous epithelium in the gut and skin...
September 2, 2016: Anatomical Science International
Tomohiro Arikawa, Shengjun Liao, Hiroki Shimada, Tomoki Inoue, Hiromi Sakata-Haga, Takanori Nakamura, Toshihisa Hatta, Hiroki Shoji
Placental development and trophoblast invasion of the maternal endometrium establish the maternal-fetal interface, which is critical for the developing embryo and fetus. Herein we show that overexpression of Galectin-4 (Gal-4) during trophoblast differentiation inhibited the enlargement of Rcho-1 cells (a model for rat trophoblast differentiation) and promoted cell-cell adhesion, whereas trophoblast specific markers and MMP-9 activity were not affected. In the rat placenta, microtubule associated protein 1 light chain 3 alpha (LC3) protein, an autophagy marker, is highly expressed on the maternal side of the decidua where Gal-4 expression is weak...
2016: Scientific Reports
Chin-Hsien Tsai, Sheue-Fen Tzeng, Tai-Kuang Chao, Chia-Yun Tsai, Yu-Chih Yang, Ming-Ting Lee, Jiuan-Jiuan Hwang, Yu-Ching Chou, Mong-Hsun Tsai, Tai-Lung Cha, Pei-Wen Hsiao
Metastatic prostate cancer continues to pose a difficult therapeutic challenge. Prostate cancer progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events is uncertain. Here we report spontaneous metastasis of human prostate cancer xenografts that express high levels of galectin-4 along with genetic signatures of EGFR-HER2 signaling and O-glycosylation. Galectin-4 expression in clinical specimens of prostate cancer correlated with poor patient survival...
October 1, 2016: Cancer Research
Zhan-Qi Cao, Xiu-Li Guo
Galectin-4, a tandem repeat member of the β-galactoside-binding proteins, possesses two carbohydrate-recognition domains (CRD) in a single peptide chain. This lectin is mostly expressed in epithelial cells of the intestinal tract and secreted to the extracellular. The two domains have 40% similarity in amino acid sequence, but distinctly binding to various ligands. Just because the two domains bind to different ligands simultaneously, galectin-4 can be a crosslinker and crucial regulator in a large number of biological processes...
May 2016: Protein & Cell
Mattias Block, Johan Mölne, Hakon Leffler, Lars Börjesson, Michael E Breimer
INTRODUCTION: The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity...
2016: BioMed Research International
Khuchtumur Bum-Erdene, Hakon Leffler, Ulf J Nilsson, Helen Blanchard
Galectin-4 is a tandem-repeat galectin with two distinct carbohydrate recognition domains (CRD). Galectin-4 is expressed mainly in the alimentary tract and is proposed to function as a lipid raft and adherens junction stabilizer by its glycan cross-linking capacity. Galectin-4 plays divergent roles in cancer and inflammatory conditions, either promoting or inhibiting each disease progression, depending on the specific pathological condition. The study of galectin-4's ligand-binding profile may help decipher its roles under specific conditions...
2016: Scientific Reports
Reham Helwa, Mohamed Ramadan, Abdel-Hady A Abdel-Wahab, Stian Knappskog, Andrea S Bauer
Galectin-4 is a member of the galectin family which consists of 15 galactoside-binding proteins. Previously, galectin-4 has been shown to have a role in cancer progression and metastasis and it is found upregulated in many solid tumours, including colorectal cancer (CRC). Recently, the role in the metastatic process was suggested to be via promoting cancer cells to adhere to blood vascular endothelium. In the present study, the regulatory region of LGALS4 (galectin-4) in seven colon cell lines was investigated with respect to genetic variation that could be linked to expression levels and therefore a tumourigenic effect...
July 2016: Mutagenesis
Xiaodong Li, Wenwei Hu, Xiao Zheng, Chu Zhang, Peng Du, Zhuojun Zheng, Yan Yang, Jun Wu, Mei Ji, Jingting Jiang, Changping Wu
BACKGROUND: Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and -PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy. MATERIAL AND METHODS: Literatures were searched and collected in Medline/PubMed. RESULTS: LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules...
November 2015: Acta Oncologica
Gabriela da Silva Cruz, Ana Luiza Dias Angelo, Ticiana Ferreira Larocca, Carolina Thé Macedo, Márcia Noya-Rabelo, Luís Claudio Lemos Correia, Jorge Andion Torreão, Bruno Solano de Freitas Souza, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares
BACKGROUND: Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated...
November 2015: Arquivos Brasileiros de Cardiologia
Mengru Wu, Yuejie Zhu, Jing Zhao, Haiquan Ai, Qiaoqiao Gong, Jia Zhang, Junda Zhao, Qingli Wang, Xiaoling La, Jianbing Ding
This study is to investigate the mechanism of unexplained recurrent spontaneous abortion (URSA). A total of 35 cases of URSA patients (URSA group), 20 cases with normal pregnancy (normal pregnancy group) and 20 healthy non-pregnancy candidates (healthy control group) were enrolled in this study. Enzyme linked immunosorbent assay (ELISA) method was used for detection of serum soluble Tim-3 (sTim3) and Galectin-9. Cytokine bead array (CBA) determination method was used to detect IFN-γ and IL-4 expression levels...
2015: International Journal of Clinical and Experimental Medicine
James F Sampson, Amol Suryawanshi, Wei-Sheng Chen, Gabriel A Rabinovich, Noorjahan Panjwani
Galectins (Gals) have emerged as potent immunoregulatory molecules that control chronic inflammation through distinct mechanisms. Gal-8, a tandem-repeat type Gal with unique preference for α2,3-sialylated glycans, is ubiquitously expressed, but little is known about its role in T-cell differentiation. Here we report that Gal-8 promotes the polyclonal differentiation of primary mouse regulatory T (Treg) cells in vitro. We further show that Gal-8 also facilitates antigen-specific differentiation of Treg cells, and that Treg cells polarized in the presence of Gal-8 express cytotoxic T-lymphocyte antigen-4 and interleukin (IL)-10 at a higher frequency than control Treg cells, and efficiently inhibit proliferation of activated T-cells in vitro...
February 2016: Immunology and Cell Biology
Satwat Hashmi, Suhail Al-Salam
Galectin-1 (GAL-1) belongs to the family of β-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT-PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery...
2015: International Journal of Clinical and Experimental Pathology
Frederick Odun-Ayo, John Mellem, Thajasvarie Naicker, Lalini Reddy
BACKGROUND: Increased intake of probiotic dietary fibre reduces colonic cancer risk. Modified citrus pectin (MCP) requires optimal bioactivity to inhibit galectin-3 (GAL-3) and vascular endothelial growth factor (VEGF). This study evaluated the preventative effect of modified pectin alginate (MCPA) probiotic microbeads on azoxymethane (AOM)-induced colonic carcinogenesis in Balb/c mice. MATERIALS AND METHODS: Optimization of AOM dose duration: 10-15 mg/kg was administered for 2-4 weeks...
September 2015: Anticancer Research
Elisabeth Lippert, Manuela Stieber-Gunckel, Nadja Dunger, Werner Falk, Florian Obermeier, Claudia Kunst
BACKGROUND: We recently identified galectin-3 (gal-3) as a new and strong fibroblast activator produced by colonic epithelial cells. Very little is known about the influence of gal-3 in inflammatory bowel disease. We, therefore, investigated the impact of gal-3 on dextran sodium sulfate (DSS)-induced colitis in a mouse model. METHODS: Colonic lamina propria fibroblasts of healthy controls were used for co-incubation studies of gal-3 with gal-1, TGF-β1, IFNγ, IL-4 and IL-10...
2015: Digestion
Anne Mobergslien, Vlada Vasovic, Geir Mathiesen, Lasse Fredriksen, Phuong Westby, Vincent G H Eijsink, Qian Peng, Mouldy Sioud
Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice...
2015: Human Vaccines & Immunotherapeutics
María T Elola, Ada G Blidner, Fátima Ferragut, Candelaria Bracalente, Gabriel A Rabinovich
Galectins are a family of β-galactoside-binding lectins carrying at least one consensus sequence in the carbohydrate-recognition domain. Properties of glycosylated ligands, such as N- and O-glycan branching, LacNAc (N-acetyl-lactosamine) content and the balance of α2,3- and α2,6-linked sialic acid dramatically influence galectin binding to a preferential set of counter-receptors. The presentation of specific glycans in galectin-binding partners is also critical, as proper orientation and clustering of oligosaccharide ligands on multiple carbohydrate side chains increase the binding avidity of galectins for particular glycosylated receptors...
July 1, 2015: Biochemical Journal
Pierpaolo Trimboli, Leo Guidobaldi, Stefano Amendola, Naim Nasrollah, Francesco Romanelli, Daniela Attanasio, Giovanni Ramacciato, Enrico Saggiorato, Stefano Valabrega, Anna Crescenzi
Core needle biopsy (CNB) has been recently described as an accurate second-line test in thyroid inconclusive cytology (FNA). Here we retrospectively investigated the potential improvement given by Galectin-3, Cytokeratin-19, and HBME-1 on the accuracy of CNB in thyroid nodules with prior indeterminate FNA report. The study included 74 nodules. At CNB diagnosis, 15 were cancers, 40 were benign, and 19 had uncertain/non-diagnostic CNB report. The above immunohistochemical (IHC) panel was analyzed in all cases...
April 2016: Endocrine
Isaac Eliaz, Elaine Weil, Julie-Ann Dutton, Audrey E McCalley, Barbie Nolte, Patrick M Moriarty
BACKGROUND: Plasma galectin-3 (Gal-3) is elevated in, and drives, diverse systemic inflammatory disorders, including cancer, cardiovascular diseases, and diabetes. Circulating Gal-3 promotes tumorigenesis and metastasis, as well as fibrotic remodeling, and is a promising therapeutic target. Apheresis has proven utility in reducing circulating disease-promoting substances, exemplified by the success of lipoprotein apheresis (LA) in abrogating cardiovascular disease progression in drug-refractory hypercholesterolemia patients...
August 2016: Journal of Clinical Apheresis
James F Sampson, Eiichi Hasegawa, Lama Mulki, Amol Suryawanshi, Shuhong Jiang, Wei-Sheng Chen, Gabriel A Rabinovich, Kip M Connor, Noorjahan Panjwani
Galectins have emerged as potent immunoregulatory agents that control chronic inflammation through distinct mechanisms. Here, we report that treatment with Galectin-8 (Gal-8), a tandem-repeat member of the galectin family, reduces retinal pathology and prevents photoreceptor cell damage in a murine model of experimental autoimmune uveitis. Gal-8 treatment increased the number of regulatory T cells (Treg) in both the draining lymph node (dLN) and the inflamed retina. Moreover, a greater percentage of Treg cells in the dLN and retina of Gal-8 treated animals expressed the inhibitory coreceptor cytotoxic T lymphocyte antigen (CTLA)-4, the immunosuppressive cytokine IL-10, and the tissue-homing integrin CD103...
2015: PloS One
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