Dexamethasone Contributes to the Side Effects in Glioblastoma Treatment

| Oncology
Alexandra Y. Tsidulko,1 Tatyana M. Pankova,1 Cynthia Bezier,2 Gabin de la Bourdannaye,3 Anastasia V. Suhovskih,1 Galina M. Kazanskaya,4 Svetlana V. Aidagulova,5 *Elvira V. Grigorieva1

The authors have declared no conflicts of interest.


This work was funded by a research grant from the Russian Scientific Foundation (grant RSF No. 16-15-10243).

EMJ Oncol. ;5[1]:38-39. Abstract Review No. AR1.

Each article is made available under the terms of the .

Glioblastoma (GBM) is the most common and malignant primary brain tumour and is characterised by the active invasion of tumour cells into surrounding brain tissue.1 The invasiveness of GBM cells depends on various factors, such as tumour cell motility, cell-cell cohesion, cell-extracellular matrix (ECM) adhesion, and the structure of ECM.2 The corticosteroid drug dexamethasone (DXM) is often used before surgery and during adjuvant therapy to alleviate cerebral oedema; however, the effects of DXM during anti-GBM treatment remain controversial.3,4 Despite the growing interest in the effects of DXM in antiglioma therapy, there are no studies on its effects on the ECM of normal brain tissue and thus its influence on tumour invasion has not been comprehensively investigated.

In this study, we investigated the effects of DXM on brain ECM in ex vivo organotypic brain tissue culture and an in vivo experimental animal model using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. As the ECM of the brain tissue consists mainly of hyaluronic acid and complex protein-carbohydrate molecules, named proteoglycans (PG), the expression levels of the main PG in the normal brain tissue were determined before and after treatment with different DXM doses and regimens. According to RT-PCR analysis, syndecan-1, glypican-1, decorin, biglycan, and lumican were shown to be the most expressed PG in rat brain tissue in both ex vivo and in vivo models. In the ex vivo organotypic hippocampus culture, DXM treatment led to dose-dependent suppression of brevican, perlecan, and biglycan expression, and an increase in expression of glypican-1, neural/glial antigen 2, and versican. As different brain zones have specific expression patterns of PG, we analysed the effect of different doses and treatment regimens of DXM on PG in the rat cortex and hippocampus in vivo. Low-dose DXM treatment led to a significant decrease in the expression of most PG in the cortex but a 3-fold increase in syndecan-1, perlecan, and brevican expression in the hippocampus. Treatment with a high dose of DXM resulted in a 2–6-fold increase in the expression of most PG in both brain zones. Long-term treatment led to the most dramatic changes in PG expression on both messenger RNA and protein levels, completely changing their expression patterns.

Taken together, the data show that DXM treatment significantly affects PG expression in normal brain tissue. High doses of DXM and long-term treatment lead to the most dramatic alteration of PG composition in brain ECM. As extracellular PG play an important role in glioma cell proliferation and invasion, such alterations can create the appropriate microenvironmental niche for cancer cell proliferation and tumour progression. In conclusion, the revealed effects of DXM on tumour-surrounding normal brain tissue suggest that DXM treatment might contribute to the negative side effects of the anti-glioma therapy, and the dose and treatment regimen are principally important.

Louis DN et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97-109.Erratum in: Acta Neuropathol. 2007;114(5):547. Vehlow A, Cordes N. Invasion as target for therapy of glioblastoma multiforme. Biochim Biophys Acta. 2013; 1836(2):236-44. Shannon S et al. Dexamethasone-mediated activation of fibronectin matrix assembly reduces dispersal of primary human glioblastoma cells. PLoS One. 2015;10(8):e0135951. Sur P et al. Dexamethasone decreases temozolomideinduced apoptosis in human gliobastoma T98G cells. Glia. 2005; 50(2):160-7.
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