Nov 21, 2015

Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hee-Young JeonHyunggee Kim

Abstract

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 po...Continue Reading

Mentioned in this Paper

TP53 gene
Biological Markers
Glioblastoma Multiforme
Standard of Care
Gene Expression Regulation, Neoplastic
Co-treatment
Cell Aging
GLB1
Cdkn1a
Transcription, Genetic

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