Journal of Neuro-Oncology

, Volume 91, Issue 2, pp 157–164 | Cite as

Inflammatory cytokine modulation of matrix metalloproteinase expression and invasiveness of glioma cells in a 3-dimensional collagen matrix

  • Susobhan Sarkar
  • V. Wee Yong
Laboratory Investigation - human/Animal Tissue


Glioma invasiveness is accomplished in part by matrix metalloproteinases (MMPs) which remodel the constraints of the three dimensional (3D) matrix of the brain parenchyma. Tissue culture studies have advanced knowledge of glioma invasiveness but the majority of studies have used a two dimensional (2D) monolayer culture system which does not reproduce the spatial constraints of invasiveness in vivo. Here, we have used a 3D matrix of type I collagen (CL) gel to address glioma invasiveness in vitro. We show that in 3D CL matrix, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), cytokines which are elevated in gliomas in vivo, increased glioma cell invasiveness with correspondent elevation of MMP-2 and MMP-9. Cytokine-stimulated glioma invasiveness was blocked by three pharmacological metalloproteinase inhibitors and by small interfering RNAs to MMP-2. Thus, in 3D matrix of CL, MMP-2 expression is modulated by inflammatory cytokines with the concomitant increase in glioma invasiveness.


Extracellular matrix Inflammation Invasiveness Metalloproteinase MMP 



This study was supported by an operating grant from the Canadian Institutes of Health Research.


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Department of OncologyUniversity of CalgaryCalgaryCanada
  2. 2.Department of Clinical NeurosciencesUniversity of CalgaryCalgaryCanada

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