The effect of dexamethasone on glioblastoma-associated stromal cells

Purpose: The corticosteroid dexamethasone has been used for decades in the management of brain tumor-associated edema. Corticosteroids can be associated with a plethora of side effects. Additionally, no equally effective agents exist for managing neurological symptoms. Furthermore, it hasnÕt been identified yet the effect of dexamethasone on glioma/stromal cells or how it shapes the course of the disease. We hypothesize that dexamethasone exerts its effect by modulating tumor-associated stromal cell function such as microglia.

Methods: PDGF-driven gliomas were generated using RCAS/Ntva system.ÊIn vivo studies were conducted on mice treated with dexamethasone and/or ionizing radiation (IR). Gene expression studies were performed to assess the effect of dexamethasone on tumor cells and microglia using the Illumina mouse ref8 array. Finally, in vitro studies were conducted using glioma cultures to validate in vivo findings.

Results: Immunohistochemical studies demonstrated that dexamethasone could alter the characteristics but not the percentage of iba-1 expression (microglia) in brain tumor tissue. Mice that have been pretreated with dexamethasone followed by IR had a significant shorter survival time compared to mice treated with IR only. Furthermore, microglia gene expression data showed a modulation of a few inflammatory cytokines that might contribute in tumor progression after dexamethasone treatment. Finally, in vitroÊstudies suggested that dexamethasone might influence stem cell characteristics.

Conclusion: In summary, our data suggests that dexamethasoneÊmodulates the course of glioma possibly through a tumor-microenvironment interaction. Dexamethasone shortened the animal survival rate when combined with IR.ÊFinally, this study shed the light on the clinical importance of dexamethasoneÕs mechanism of action and hence the development of new therapies to manage neuro-symptoms.