title: Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related Siglecs.
abstract: Lectin galactoside-binding soluble 3 binding protein (LGALS3BP, also called Mac-2 binding protein) is a heavily glycosylated secreted molecule that has been shown previously to be up-regulated in many cancers and has been implicated in tumor metastatic processes, as well as in other cell adhesion and immune functions. The CD33-related subset of sialic acid-binding immunoglobulin-like lectins (Siglecs) consists of immunomodulatory molecules that have recently been associated with the modulation of immune responses to cancer. Because up-regulation of Siglec ligands in cancer tissue has been observed, the characterization of these cancer-associated ligands that bind to inhibitory CD33-related Siglecs could provide novel targets for cancer immunomodulatory therapy. Here we used affinity chromatography of tumor cell extracts to identify LGALS3BP as a novel sialic acid-dependent ligand for human Siglec-9 and for other immunomodulatory Siglecs, such as Siglec-5 and Siglec-10. In contrast, the mouse homolog Siglec-E binds to murine LGALS3BP with lower affinity. LGALS3BP has been observed to be up-regulated in human colorectal and prostate cancer specimens, particularly in the extracellular matrix. Finally, LGALS3BP was able to inhibit neutrophil activation in a sialic acid- and Siglec-dependent manner. These findings suggest a novel immunoinhibitory function for LGALS3BP that might be important for immune evasion of tumor cells during cancer progression.
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 heinz.laeubli@unibas.ch.
authors.forename: Heinz
authors.initials: H
authors.lastname: Läubli
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Frederico
authors.initials: F
authors.lastname: Alisson-Silva
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Michal A
authors.initials: MA
authors.lastname: Stanczak
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Shoib S
authors.initials: SS
authors.lastname: Siddiqui
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Liwen
authors.initials: L
authors.lastname: Deng
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Andrea
authors.initials: A
authors.lastname: Verhagen
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
authors.affiliation: From the Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093 a1varki@ucsd.edu.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019139:Tumor Escape; D015854:Up-Regulation / Q000276:immunology; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins
keywords: Cancer; Galectin; Glycobiology; LGALS3BP; Sialic Acid; Siglecs; Tumor Immunology