Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Endothelial integrin α3β1 stabilizes carbohydrate-mediated tumor/endothelial cell adhesion and induces macromolecular signaling complex formation at the endothelial cell membrane.

Abstract: // Olga V. Glinskii 1,2 , Feng Li 1,2 , Landon S. Wilson 3 , Stephen Barnes 3 , Kate Rittenhouse-Olson 4 , Joseph J. Barchi, Jr. 5 , Kenneth J. Pienta 6 , Vladislav V. Glinsky 1,2 1 Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 2 Department of Pathology and Anatomical Sciences and the Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 3 Department of Pharmacology and Toxicology and Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 4 Department of Biotechnical and Clinical Laboratory Sciences and the Department of Microbiology, University of Buffalo, Buffalo, NY 5 Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD 6 Department of Urology, The James Buchanan Brady Urological Institute, Departments of Oncology and Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD Correspondence: Vladislav V. Glinsky, email: // Keywords : tumor metastasis, adhesion, Thomsen-Friedenreich antigen, galectin, integrin Received : February 10, 2014 Accepted : March 19, 2014 Published : March 20, 2014 Abstract Blood borne metastatic tumor cell adhesion to endothelial cells constitutes a critical rate-limiting step in hematogenous cancer metastasis. Interactions between cancer associated carbohydrate Thomsen-Friedenreich antigen (TF-Ag) and endothelium-expressed galectin-3 (Gal-3) have been identified as the leading molecular mechanism initiating tumor/endothelial cell adhesion in several types of cancer. However, it is unknown how these rather weak and transient carbohydrate/lectin mediated interactions are stabilized. Here, using Western blot and LC tandem mass spectrometry analyses of pull-downs utilizing TF-Ag loaded gold nanoparticles, we identified Gal-3, endothelial integrin α3β1, Src kinase, as well as 5 additional molecules mapping onto focal adhesion pathway as parts of the macromolecular complexes formed at the endothelial cell membranes downstream of TF-Ag/Gal-3 interactions. In a modified parallel flow chamber assay, inhibiting α3β1 integrin greatly reduced the strength of tumor/endothelial cell interactions without affecting the initial cancer cell adhesion. Further, the macromolecular complex induced by TF-Ag/Gal-3/α3β1 interactions activates Src kinase, p38, and ERK1/2, pathways in endothelial cells in a time- and α3β1-dependent manner. We conclude that, following the initial metastatic cell attachment to endothelial cells mediated by TF-Ag/Gal-3 interactions, endothelial integrin α3β1 stabilizes tumor/endothelial cell adhesion and induces the formation of macromolecular signaling complex activating several major signaling pathways in endothelial cells.

F-fucoidan from Saccharina japonica is a novel inducer of galectin-9 and exhibits anti-allergic activity.

Abstract: Fucoidan is a sulfated polysaccharide from brown sea algae. In the present study, it was demonstrated that oral administration of F-fucoidan from Saccharina japonica possessed anti-allergic effects using the passive cutaneous anaphylaxis reaction, but not by intraperitoneal administration. The inhibitory mechanism was dependent on galectin-9, which belongs to a soluble lectin family that recognizes β-galactoside and prevents IgE binding to mast cells. The anti-allergy properties of F-fucoidan were cancelled by an intravenous dose of anti-galectin-9 antibody or lactose, which bind competitively with galectin-9 before the passive cutaneous anaphylaxis reaction. F-fucoidan increased the expression level of galectin-9 mRNA in intestinal epithelial cells and serum galectin-9 levels. Oral treatment with F-fucoidan suppressed allergic symptoms through the induction of galectin-9. This is the first report that F-fucoidan can induce the secretion of galectin-9.

Galectins: novel anti-inflammatory drug targets

Abstract: Galectins are a protein family defined by their affinity for beta-galactosides and consensus sequences. They are pleiotropic regulators involved in a multitude of functions, both in and out of the cell. Extracellularly, they have the potential to bind to various surface receptors on a variety of cell types as well as extracellular matrix (ECM) proteins, thus causing cell activation or apoptosis, modulating cell adhesion and inducing cell migration. Intracellularly, they can regulate cell growth, apoptosis and cell cycle progression. Galectins are either pro-inflammatory or anti-inflammatory. Some, such as galectin-1, may be employed as anti-inflammatory agents, while others, such as galectin-3, are evidently suitable targets for anti-inflammatory drugs. The extracellular functions of galectins involve their lectin-carbohydrate interactions and thus their carbohydrate ligands or mimetics would be suitable inhibitors. While the intracellular functions of galectins do not appear to engage lectin-carbohydrate interactions, the carbohydrate-binding sites of these proteins may still be involved. Therefore, the same inhibitors may be used regardless of whether intracellular or extracellular galectins are to be targeted.