Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance.
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.
['Kostopoulou|Ourania N|ON|', 'Mohammad|Abdul-Aleem|AA|', 'Bartek|Jiri|J|', 'Winter|Julia|J|', 'Jung|Masany|M|', 'Stragliotto|Giuseppe|G|', 'Söderberg-Nauclér|Cecilia|C|', 'Landázuri|Natalia|N|0000-0002-7182-8767']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000970:Antineoplastic Agents D001921:Brain D001929:Brain Edema D001932:Brain Neoplasms D049109:Cell Proliferation D059186:Chemoradiotherapy, Adjuvant D003907:Dexamethasone D018572:Disease-Free Survival D019008:Drug Resistance, Neoplasm D005260:Female D005909:Glioblastoma D005938:Glucocorticoids D006801:Humans D008297:Male D008875:Middle Aged D009364:Neoplasm Recurrence, Local D014411:Neoplastic Stem Cells D019635:Neurosurgical Procedures D061251:Primary Cell Culture D011379:Prognosis D013312:Stress, Physiological D016896:Treatment Outcome D014407:Tumor Cells, Cultured
glucocorticoid chemotherapy glioblastoma cancer tumor recurrence