Cancer-associated glycoforms of gelatinase B exhibit a decreased level of binding to galectin-3

Simon A Fry, Philippe E Van den Steen, Louise Royle, Mark R Wormald, Anthony J Leathem, Ghislain Opdenakker, James M McDonnell, Raymond A Dwek, Pauline M Rudd

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Gelatinase B (MMP-9) and galectin-3 are widely known to participate in tumor cell invasion and metastasis. Glycans derived from MMP-9 expressed in MCF-7 breast cancer and THP-1 myeloid leukemia cells were compared with those from MMP-9 expressed in natural neutrophils. The many O-linked glycans of neutrophil gelatinase B presented a cluster of mainly galactosylated core II structures, 46% of which were ligands for galectin-3; 11% contained two to three N-acetyllactosamine repeating units that are high-affinity ligands for the lectin. The glycan epitopes thus provide MMP-9 with both high-affinity and (presumably) high-avidity interactions with galectin-3. In contrast, the O-glycans released from MMP-9 expressed in MCF-7 and THP-1 cells were predominantly sialylated core I structures. Only 10% of MCF-7 and THP-1 gelatinase B O-glycans were ligands for galectin-3 and contained only a maximum single N-acetyllactosamine repeat. Consistent with the glycan analysis, surface plasmon resonance binding assays indicated that the cancer-associated glycoforms of MMP-9 bound galectin-3 with an affinity and avidity significantly reduced compared with those of the natural neutrophil MMP-9. Galectin-3 exists as a multimer that also binds laminin, providing a means of localizing neutrophil MMP-9 in the extracellular matrix (ECM). The analytical data presented here suggest that MMP-9 glycoforms secreted by tumor cells are unlikely to be tethered at the site of secretion, thus promoting more extensive cleavage of the ECM and providing a rationale for the contribution that gelatinase B makes to cancer cell metastasis.
Original languageEnglish
Pages (from-to)15249-15258
Number of pages10
JournalBiochemistry
Volume45
Issue number51
DOIs
Publication statusPublished - 26 Dec 2006

Keywords

  • Animals
  • Breast Neoplasms
  • Carbohydrate Conformation
  • Cattle
  • Cell Line, Tumor
  • Down-Regulation
  • Extracellular Matrix
  • Galectin 3
  • Glycosylation
  • Humans
  • Isoenzymes
  • Leukemia, Myeloid
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neutrophils
  • Polysaccharides
  • Protein Binding
  • Surface Plasmon Resonance

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