Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype
| Autor: | Se Yeong Oh, Jun Kyum Kim, Hee Young Jeon, Jae-Yong Lee, Hyunggee Kim, Sung Chan Kim, Jae Bong Park, Seok Won Ham, Jaebong Kim |
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| Rok vydání: | 2015 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Senescence Pathology medicine.medical_specialty medicine.medical_treatment Biology urologic and male genital diseases Mice 03 medical and health sciences Cell Line Tumor medicine Animals Humans Survival rate Cellular Senescence Cell Proliferation Chemotherapy urogenital system Cell growth Cell Cycle NF-kappa B Dose-Response Relationship Radiation General Medicine Cell cycle Phenotype female genital diseases and pregnancy complications nervous system diseases Gene Expression Regulation Neoplastic Radiation therapy Disease Models Animal 030104 developmental biology Heterografts Glioblastoma Cell aging |
| Zdroj: | Tumor Biology. 37:5857-5867 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-015-4439-2 |
| Popis: | Glioblastoma multiforme (GBM) is one of the most aggressive and fatal primary brain tumors in humans. The standard therapy for the treatment of GBM is surgical resection, followed by radiotherapy and/or chemotherapy. However, the frequency of tumor recurrence in GBM patients is very high, and the survival rate remains poor. Delineating the mechanisms of GBM recurrence is essential for therapeutic advances. Here, we demonstrate that irradiation rendered 17-20 % of GBM cells dead, but resulted in 60-80 % of GBM cells growth-arrested with increases in senescence markers, such as senescence-associated beta-galactosidase-positive cells, H3K9me3-positive cells, and p53-p21(CIP1)-positive cells. Moreover, irradiation induced expression of senescence-associated secretory phenotype (SASP) mRNAs and NFκB transcriptional activity in GBM cells. Strikingly, compared to injection of non-irradiated GBM cells into immune-deficient mice, the co-injection of irradiated and non-irradiated GBM cells resulted in faster growth of tumors with the histological features of human GBM. Taken together, our findings suggest that the increases in senescent cells and SASP in GBM cells after irradiation is likely one of main reasons for tumor recurrence in post-radiotherapy GBM patients. |
| Databáze: | OpenAIRE |
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