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Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression

D S Markovic1, K Vinnakota, N van Rooijen

  • 1Max Delbrück Center for Molecular Medicine, Cellular Neuroscience, Robert Rössle Str. 10, 13125 Berlin, Germany.

Brain, Behavior, and Immunity
|February 18, 2011
PubMed

Insights

The antibiotic minocycline reduces glioma growth by blocking microglia-mediated invasion. This suggests minocycline as a potential adjuvant therapy for malignant gliomas.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Molecular Biology

Background:

  • Glioma cells promote tumor-associated microglia (TAM) to express membrane type 1 matrix metalloprotease (MT1-MMP).
  • MT1-MMP facilitates glioma invasion through matrix degradation.
  • Targeting this pathway presents a therapeutic opportunity.

Purpose of the Study:

  • To investigate the effect of minocycline on MT1-MMP expression in microglia.
  • To evaluate minocycline's efficacy in reducing glioma growth in vitro and in vivo.
  • To determine the role of microglia in minocycline's anti-glioma effects.

Main Methods:

  • Cultured microglia were stimulated with glioma conditioned medium.
  • MT1-MMP expression and activity were assessed.
  • Glioma growth was measured in organotypic brain slice and orthotopic mouse models.
  • Minocycline was administered orally in drinking water.

Main Results:

  • Minocycline inhibited MT1-MMP expression and activity in stimulated microglia.
  • Minocycline significantly reduced glioma growth in brain slice preparations, dependent on microglia presence.
  • Oral minocycline administration markedly reduced glioma growth in a mouse model.
  • MT1-MMP expression in microglia within gliomas was significantly attenuated by minocycline treatment.

Conclusions:

  • Minocycline effectively blocks MT1-MMP mediated glioma invasion.
  • Minocycline demonstrates significant anti-glioma efficacy in preclinical models.
  • Minocycline is a promising candidate for adjuvant therapy in malignant gliomas.

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