Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype

Hee Young Jeon, Jun Kyum Kim, Seok Won Ham, Se Yeong Oh, Jaebong Kim, Jae Bong Park, Jae Yong Lee, Sung Chan Kim, Hyunggee Kim

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

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-p21CIP1-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.

Original languageEnglish
Pages (from-to)5857-5867
Number of pages11
JournalTumor Biology
Volume37
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Bibliographical note

Funding Information:
We would like to thank all the members of the Cell Growth Regulation Laboratory for their helpful discussion and technical assistance. This work was supported by the National Nuclear Technology Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT, and Future Planning (No. 2013M2A2A7042530 to H. Kim), and a research grant (to S.Y. Oh) funded by the Institute of Life Science and Natural Resources at Korea University.

Publisher Copyright:
© 2015, International Society of Oncology and BioMarkers (ISOBM).

Keywords

  • Glioblastoma multiforme
  • Radiotherapy
  • Recurrence
  • Senescence
  • Senescence-associated secretory phenotype

ASJC Scopus subject areas

  • Cancer Research

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