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

  • Laboratory Investigation - human/Animal Tissue
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Abstract

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Oncology, University of Calgary, 3330 Hospital Drive, Calgary, AB, Canada, T2N 4N1

    Susobhan Sarkar & V. Wee Yong

  2. Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive, Calgary, AB, Canada, T2N 4N1

    V. Wee Yong

Authors
  1. Susobhan Sarkar
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  2. V. Wee Yong
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Correspondence to V. Wee Yong.

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Sarkar, S., Yong, V.W. Inflammatory cytokine modulation of matrix metalloproteinase expression and invasiveness of glioma cells in a 3-dimensional collagen matrix. J Neurooncol 91, 157–164 (2009). https://doi.org/10.1007/s11060-008-9695-1

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  • DOI: https://doi.org/10.1007/s11060-008-9695-1

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