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

Lo Cicero, Alessandra, Majkowska, Iwona, Nagase, Hideaki, Di Liegro, Italia and Troeberg, Linda (2012) Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity. Matrix Biology, 31 (4). pp. 229-233. ISSN 0945-053X

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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.

    Item Type: Article
    Additional Information: Copyright © 2012 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
    Uncontrolled Keywords: metabolism,adamts5 protein,metabolism,cell physiological phenomena,enzymology,pharmacology,metabolism,enzyme activation,drug effects,humans,enzymology,proteolysis,metabolism,pathology,pharmacology
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Related URLs:
    Depositing User: LivePure Connector
    Date Deposited: 08 Jan 2019 13:30
    Last Modified: 08 Jan 2019 20:30
    URI: https://ueaeprints.uea.ac.uk/id/eprint/69491
    DOI: 10.1016/j.matbio.2012.02.005

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