Lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a tumor-associated immunomodulatory ligand for CD33-related Siglecs

Heinz Läubli, Frederico Alisson-Silva, Michal A Stanczak, Shoib S Siddiqui, Liwen Deng, Andrea Verhagen, Nissi Varki, Ajit Varki

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)33481-91
Number of pages11
JournalThe Journal of biological chemistry
Issue number48
Publication statusPublished - 28 Nov 2014


  • Animals
  • Antigens, Neoplasm/biosynthesis
  • Biomarkers, Tumor/biosynthesis
  • Carrier Proteins/biosynthesis
  • Colorectal Neoplasms/genetics
  • Female
  • Gene Expression Regulation, Neoplastic/immunology
  • Glycoproteins/biosynthesis
  • HEK293 Cells
  • Humans
  • Immunologic Factors/biosynthesis
  • Male
  • Mice
  • Neoplasm Proteins/genetics
  • Prostatic Neoplasms/genetics
  • Sialic Acid Binding Ig-like Lectin 3/genetics
  • Tumor Escape
  • Up-Regulation/immunology


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