Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

1490 - Dose- and regimen-dependent effects of dexamethasone on extracellular matrix of brain tissue

Date

11 Sep 2017

Session

Poster display session

Topics

Cancer Biology

Presenters

Alexandra Tsidulko

Citation

Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361

Authors

A.Y. Tsidulko1, T.M. Pankova2, C. Bezier3, G. de La Bourdannaye4, A.V. Suhovskih1, G.M. Kazanskaya5, S.V. Aidagulova6, E. Grigorieva1

Author affiliations

  • 1 Laboratory Of Molecular Mechanisms Of Carcinogenesis, Institute of Molecular Biology and Biophysics SB RAMS, 630117 - Novosibirsk/RU
  • 2 Laboratory Of Central Regulation Mechanisms, Institute of Molecular Biology and Biophysics SB RAMS, 630117 - Novosibirsk/RU
  • 3 Molecular And Cellular Biology, Pierre et Marie Curie University, 75 005 - Paris/FR
  • 4 Biochemical Engineering, Institut national des sciences appliquées de Toulouse, Toulouse/FR
  • 5 Laboratory Of Experimental Surgery And Morphology, Novosibirsk Research Institute of Circulation Pathology, Novosibirsk/RU
  • 6 Laboratory Of Cell Biology, Novosibirsk State Medical University, Novosibirsk/RU
More

Resources

Abstract 1490

Background

Dexamethasone (DXM) is commonly used in the management of glioma patients to treat intracranial edema but patients often suffer from its side effects. The molecular mechanisms of these side effects are poorly studied. DXM seems to affect extracellular matrix (ECM) especially proteoglycans (PGs) known to be a major component of the ECM in brain tissue. The aim of our study was to investigate if the effects of DXM on brain tissue PGs depend on the treatment regimen or DXM dose.

Methods

Effects of different doses and regimens of DXM treatment on the brain ECM were studied using RT-PCR and IHC in the ex vivo model of organotypic brain tissue culture and in vivo experimental animal model. The ex vivo organotypic culture model was chosen instead of in vitro cell culture model as it represents the real 3D structure of the tissue and can be used to study ECM.

Results

The most expressed PGs in rat brain tissue were syndecan-1, glypican-1, decorin, biglycan and lumican. DXM treatment of organotypic hippocampus culture ex vivo led to dose-dependent suppression of brevican, perlecan and biglycan expression and increase in expression of glypican-1, NG2 and versican. In the in vivo experiments, PGs demonstrated age-specific and brain zone-specific expression patterns in normal brain of Wistar rats. The effects of DXM on cortex and hippocampus of the experimental animals were dose- and regimen-dependent. Low-dose DXM treatment led to significant decrease in expression of most PGs in cortex but 3-fold increase in syndecan-1, perlecan and brevican expression in hippocampus. Treatment with high-dose DXM resulted in 2-6-fold increase in most of PGs expression in both brain zones. Long-term treatment led to the most dramatic changes in PGs expression on both mRNA and protein levels, completely changing their expression pattern.

Conclusions

Taken together, obtained data demonstrate an importance of DXM doses/regimens during antiglioma therapy. Long-term treatment and high doses of DXM lead to the most dramatic alteration of PGs composition in brain ECM creating a favorable niche for tumor growth and relapses.

Clinical trial identification

Legal entity responsible for the study

Institute of Molecular Biology and Biophysics

Funding

Russian Science Foundation (RSF grant 16-15-10243).

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.