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

• Published in: Matrix biology 2012-05, Vol.31 (4), p.229-233
• Main Authors: Lo Cicero, Alessandra, Majkowska, Iwona, Nagase, Hideaki, Di Liegro, Italia, Troeberg, Linda
• Format: Article
• Language: English
• Subjects: ADAM Proteins - metabolism; ADAMTS; ADAMTS5 Protein; Aggrecan; Aggrecans - metabolism; Brief Report; Cell Physiological Phenomena; Cytoplasmic Vesicles - enzymology; Cytoplasmic Vesicles - physiology; Dipeptides - pharmacology; Endopeptidases - metabolism; Enzyme Activation; Fibroblasts - drug effects; Fibroblasts - enzymology; Humans; Membrane vesicles; Metalloproteinase; Oligodendroglioma - enzymology; Proteolysis; Recombinant Proteins - metabolism; Rheumatic Fever - pathology; Tissue Inhibitor of Metalloproteinase-3 - pharmacology
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2012.02.005

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. ► Microvesicles are shed by numerous cell types. ► We isolated microvesicles shed by oligrodendroglioma and rheumatoid synovial fibroblasts. ► These microvesicles contained an aggrecan-degrading proteolytic activity. ► Microvesicles may thus assist cells in degrading aggrecan-rich extracellular matrices.