title: Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype.
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 post-radiotherapy GBM patients.
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.|Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Jeon
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.|Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Jun-Kyum
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Ham
authors.affiliation: Institute of Life Science and Natural Resources, Korea University, Seoul, Republic of Korea.
authors.forename: Se-Yeong
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jaebong
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Republic of Korea. biokim@hallym.ac.kr.
authors.forename: Sung-Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. hg-kim@korea.ac.kr.|Institute of Animal Molecular Biotechnology, Korea University, Seoul, Republic of Korea. hg-kim@korea.ac.kr.
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D064593:Heterografts; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D015533:Transcriptional Activation
chemical_list: D016328:NF-kappa B
keywords: Glioblastoma multiforme; Radiotherapy; Recurrence; Senescence; Senescence-associated secretory phenotype