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

Alessandra Lo Cicero1, Iwona Majkowska, Hideaki Nagase

  • 1Dipartimento di Biomedicina sperimentale e Neuroscienze cliniche, via del Vespro 129, 90127 Palermo, Italy.

Matrix Biology : Journal of the International Society for Matrix Biology
|March 13, 2012
PubMed

Insights

Oligodendroglioma and rheumatoid fibroblast cells shed microvesicles containing aggrecanase activity. This enzyme activity, sensitive to tissue inhibitor of metalloproteinases-3 (TIMP-3), may facilitate invasion through extracellular matrices.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Extracellular Matrix Biology

Background:

  • Membrane microvesicle shedding is an active process in viable cells.
  • Oligodendroglioma and rheumatoid synovial fibroblasts are implicated in tissue degradation.

Purpose of the Study:

  • To investigate the enzymatic activity of microvesicles shed by oligodendroglioma cells.
  • To determine the role of these microvesicles in extracellular matrix degradation.

Main Methods:

  • Analysis of microvesicle shedding from oligodendroglioma cells.
  • Assay of aggrecanase activity in shed microvesicles.
  • Inhibition studies using EDTA, GM6001, and tissue inhibitors of metalloproteinases (TIMPs).
  • Detection of ADAMTS expression in oligodendroglioma cells.

Main Results:

  • Microvesicles shed by oligodendroglioma cells exhibit aggrecanase activity.
  • This activity cleaves aggrecan at metalloproteinase-sensitive sites.
  • Degradation was inhibited by EDTA, GM6001, and TIMP-3, but not TIMP-1 or TIMP-2.
  • Oligodendroglioma cells express Adamts1, Adamts4, and Adamts5.
  • Similar aggrecanase activity was observed in microvesicles from rheumatoid synovial fibroblasts.

Conclusions:

  • Shed microvesicles contain TIMP-3-sensitive aggrecanase activity, likely mediated by ADAMTS enzymes.
  • Microvesicles may contribute to the invasion of oligodendroglioma and rheumatoid synovial fibroblasts through aggrecan-rich matrices.

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