Glucocorticoids promote a glioma stem cell‐like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance

Abstract

Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to therapy and can give rise to recurrent tumors. The identification of patient-related factors that support GSCs is thus necessary to design effective therapies for GBM patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, which has been linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and GSCs. Here, we treated primary human GBM cells with dexamethasone and evaluated GC-driven changes in cell morphology, proliferation, migration, gene expression, secretory activity and growth as neurospheres. Dexamethasone treatment of GBM cells appeared to promote the development of a GSC-like phenotype and conferred resistance to physiological stress and chemotherapy. We also analyzed a potential correlation between GC treatment and tumor recurrence after surgical excision in a population-based consecutive cohort of 48 GBM patients, adjusted for differences in known prognostic factors concerning baseline and treatment characteristics. In this cohort, we found a negative correlation between GC intake and progression-free survival, regardless of the MGMT methylation status. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and may support a GSC population, which could contribute to tumor recurrence and the poor prognosis of the disease.

Longitudinal study of cognitive function in glioma patients treated with modern radiotherapy techniques and standard chemotherapy

“…We did find an association between medication of corticosteroids and impaired executive functioning. This effect may be interpreted as a result of aggressive tumor growth requiring steroid use, rather than the steroid treatment per se, but direct disease-driving effects of corticosteroids have also been discussed [26].…”

Glucocorticoids are double-edged sword in the treatment of COVID-19 and cancers

“…On the other hand, some studies found that glucocorticoids could suppress cancer proliferation through activating glucocorticoid receptor [50,51]. For example, Yao and coworkers recently demonstrated that dexamethasone inhibits pancreatic tumor growth in preclinical models.…”

Controversial roles for dexamethasone in glioblastoma – Opportunities for novel vascular targeting therapies

“…In primary GBM cell lines treated with TMZ, the addition of DEX counteracted TMZ-induced apoptosis and caused resistance to nutrient deprivation. 40–42 Furthermore, in vitro DEX administration reduced the bystander effect of the thymidine kinase/ganciclovir system in suicide-gene therapy and reduced the antitumor effect of interleukin-4. 43,44 The alkylating impact of TMZ targets the O 6 -alkylguanin in the carcinogenic lesion, which is reversed by the O 6 -methylguanine-DNA-methyltransferase (MGMT) repair enzyme.…”