期刊
INTERNATIONAL JOURNAL OF CANCER
卷 142, 期 6, 页码 1266-1276出版社
WILEY
DOI: 10.1002/ijc.31132
关键词
glucocorticoid; glioblastoma; cancer; chemotherapy; tumor recurrence
类别
资金
- BILTEMA Foundation
- Stichting af Jochnicks Foundation
- Sten A. Olssons Foundation for Research and Culture
- Ragnar Soderberg Foundation [MF14/10]
- Swedish Research Council [10350, K2007-56X-12615-10-3]
- Swedish Research Council Framework (Grant in Infections and Antibiotics) [K2014-99X-22627-01-4]
- Swedish Cancer Foundation [5044-B05-01XAB]
- Dan och Jane Olssons Foundation
- Nexttobe
- Torsten Soderberg Foundation [MF14/10]
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.
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