Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance.
Ourania N KostopoulouAbdul-Aleem MohammadJiri BartekJulia WinterMasany JungGiuseppe StragliottoCecilia Söderberg-NauclérNatalia LandázuriPublished in: International journal of cancer (2017)
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.
Keyphrases
- stem cells
- prognostic factors
- induced apoptosis
- poor prognosis
- gene expression
- cell cycle arrest
- endothelial cells
- end stage renal disease
- free survival
- newly diagnosed
- ejection fraction
- endoplasmic reticulum stress
- long non coding rna
- low dose
- squamous cell carcinoma
- dna methylation
- peritoneal dialysis
- signaling pathway
- single cell
- mass spectrometry
- physical activity
- cell death
- body mass index
- case report
- oxidative stress
- pluripotent stem cells
- risk assessment
- weight gain
- pi k akt
- genome wide
- weight loss
- patient reported