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RESEARCH PRODUCT
Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity
Hideaki NagaseAlessandra Lo CiceroItalia Di LiegroIwona MajkowskaLinda Troebergsubject
OligodendrogliomaMembrane vesicleRA rheumatoid arthritisADAMTSMatrix metalloproteinaseCell Physiological PhenomenaAdamalysin03 medical and health sciences0302 clinical medicineSettore BIO/10 - BiochimicaEndopeptidasesHumansAggrecansADAM adamalysinADAMTS a disintegrin and metalloproteinase with thrombospondin motifsMolecular BiologyMetalloproteinase030304 developmental biologyAggrecanaseTissue Inhibitor of Metalloproteinase-3MEF mouse embryonic fibroblasts0303 health sciencesMetalloproteinaseChemistryBrief ReportMVs microvesiclesADAMTSMicrovesicleCytoplasmic VesiclesDipeptidesFibroblastsMolecular biologyRecombinant ProteinsMicrovesiclesECM extracellular matrixMembrane vesiclesCell biologyEnzyme ActivationMMP matrix metalloproteinaseADAM ProteinsADAMTS4030220 oncology & carcinogenesisProteolysisADAMTS5 ProteinRheumatic FeverTIMP tissue inhibitor of metalloproteinaseAggrecandescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-05-01 |