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

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.
AuthorsAlessandra Lo Cicero, Iwona Majkowska, Hideaki Nagase, Italia Di Liegro, Linda Troeberg
JournalMatrix biology : journal of the International Society for Matrix Biology (Matrix Biol) Vol. 31 Issue 4 Pg. 229-33 (May 2012) ISSN: 1569-1802 [Electronic] Netherlands
PMID22406378 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Aggrecans
  • Dipeptides
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-3
  • Endopeptidases
  • ADAM Proteins
  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • aggrecanase
Topics
  • ADAM Proteins (metabolism)
  • ADAMTS5 Protein
  • Aggrecans (metabolism)
  • Cell Physiological Phenomena
  • Cytoplasmic Vesicles (enzymology, physiology)
  • Dipeptides (pharmacology)
  • Endopeptidases (metabolism)
  • Enzyme Activation
  • Fibroblasts (drug effects, enzymology)
  • Humans
  • Oligodendroglioma (enzymology)
  • Proteolysis
  • Recombinant Proteins (metabolism)
  • Rheumatic Fever (pathology)
  • Tissue Inhibitor of Metalloproteinase-3 (pharmacology)

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