Galectin-3 binds to CD45 on diffuse large B-cell lymphoma cells to regulate susceptibility to cell death

Clark, Mary C.; Pang, Mabel; Hsu, Daniel K.; Liu, Fu‐Tong; Vos, Sven de; Gascoyne, Randy D.; Said, Jonathan; Baum, Linda G.

doi:10.1182/blood-2012-06-438234

Cited by 81 publications

(70 citation statements)

References 50 publications

(104 reference statements)

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“…Considering that Galectin 3 is a major regulator of BCL2 function, the Raz laboratory has also advocated use of MCP for use with BH3 mimetics that are being commonly used for cancer therapy (30). One such MCP, GCS-100, has proved effective in preclinical models of multiple myeloma, lymphoma, leukemia, and solid tumors (23,77,82,132,143,144). TD139, an inhibitor targeting the glycan binding pocket of Galectin 3 has been shown to block Galectin 3 mediated endocytosis and reduce pro-inflammatory cytokines produced by dendritic cells (144)(145)(146).…”

Section: Strategies To Target Galectin 3 For Cancer Therapymentioning

confidence: 98%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

165

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Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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Section: Strategies To Target Galectin 3 For Cancer Therapymentioning

confidence: 98%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

165

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“…Gal1 binds to the T-cell-surface glycoproteins CD45, CD43, CD71 and CD7, which induces cell death and determines T-cell fate (Nguyen et al, 2001;Stillman et al, 2006). The main ligand for Gal3 on B-cell lymphoma is the phosphatase CD45; whose binding to Gal3 reduces its activity and opposes apoptosis (Clark et al, 2012). In fact, endogenous Gal3-mediated crosslinking of activated T cells was the first description of a galectin lattice that restrained T-cell receptor (TCR) mobility and reduced their sensitivity to antigen.…”

Section: T-cell Receptor and The Immune Responsementioning

confidence: 99%

The galectin lattice at a glance

Nabi

Shankar

Dennis

2015

Journal of Cell Science

271

230

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Galectins are a family of widely expressed β-galactoside-binding lectins in metazoans. The 15 mammalian galectins have either one or two conserved carbohydrate recognition domains (CRDs), with galectin-3 being able to pentamerize; they form complexes that crosslink glycosylated ligands to form a dynamic lattice. The galectin lattice regulates the diffusion, compartmentalization and endocytosis of plasma membrane glycoproteins and glycolipids. The galectin lattice also regulates the selection, activation and arrest of T cells, receptor kinase signaling and the functionality of membrane receptors, including the glucagon receptor, glucose and amino acid transporters, cadherins and integrins. The affinity of transmembrane glycoproteins to the galectin lattice is proportional to the number and branching of their N-glycans; with branching being mediated by Golgi N-acetylglucosaminyltransferasebranching enzymes and the supply of UDP-GlcNAc through metabolite flux through the hexosamine biosynthesis pathway. The relative affinities of glycoproteins for the galectin lattice depend on the activities of the Golgi enzymes that generate the epitopes of their ligands and, thus, provide a means to analyze biological function of lectins and of the 'glycome' more broadly.

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“…l'homme [34][35][36][37]. Les effets antitumoraux de ces polysaccharides ont été le plus souvent étudiés dans des cancers avancés, en association avec des anticorps monoclonaux (par exemple ipilimubab, un anti-CTLA-4), des inhibiteurs du protéasome (bortezomib), ou le 5-fluorouracile.…”

Section: Référencesunclassified