Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity

Alessandra Lo Cicero, Iwona Majkowska, Hideaki Nagase, Italia Di Liegro, Linda Troeberg

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)
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Abstract

Membrane microvesicle shedding is an active process and occurs in viable cells with no signs of apoptosis or necrosis. We report here that microvesicles shed by oligodendroglioma cells contain an 'aggrecanase' activity, cleaving aggrecan at sites previously identified as targets for adamalysin metalloproteinases with disintegrin and thrombospondin domains (ADAMTSs). Degradation was inhibited by EDTA, the metalloproteinase inhibitor GM6001 and by tissue inhibitor of metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2. This inhibitor profile indicates that the shed microvesicles contain aggrecanolytic ADAMTS(s) or related TIMP-3-sensitive metalloproteinase(s). The oligodendroglioma cells were shown to express the three most active aggrecanases, namely Adamts1, Adamts4 and Adamts5, suggesting that one or more of these enzymes may be responsible for the microvesicle activity. Microvesicles shed by rheumatoid synovial fibroblasts similarly degraded aggrecan in a TIMP-3-sensitive manner. Our findings raise the novel possibility that microvesicles may assist oligodendroglioma and rheumatoid synovial fibroblasts to invade through aggrecan-rich extracellular matrices.

Original languageEnglish
Pages (from-to)229-233
Number of pages5
JournalMatrix Biology
Volume31
Issue number4
Early online date2 Mar 2012
DOIs
Publication statusPublished - May 2012

Keywords

  • ADAM Proteins/metabolism
  • ADAMTS5 Protein
  • Aggrecans/metabolism
  • Cell Physiological Phenomena
  • Cytoplasmic Vesicles/enzymology
  • Dipeptides/pharmacology
  • Endopeptidases/metabolism
  • Enzyme Activation
  • Fibroblasts/drug effects
  • Humans
  • Oligodendroglioma/enzymology
  • Proteolysis
  • Recombinant Proteins/metabolism
  • Rheumatic Fever/pathology
  • Tissue Inhibitor of Metalloproteinase-3/pharmacology

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