Ly6G(+) inflammatory cells enable the conversion of cancer cells to cancer stem cells in an irradiated glioblastoma modelopen access
- Authors
- Jeon, Hee-Young; Ham, Seok Won; Kim, Jun-Kyum; Jin, Xiong; Lee, Seon Yong; Shin, Yong Jae; Choi, Chang-Yong; Sa, Jason K.; Kim, Se Hoon; Chun, Taehoon; Jin, Xun; Nam, Do-Hyun; Kim, Hyunggee
- Issue Date
- Oct-2019
- Publisher
- Nature Publishing Group
- Citation
- Cell Death and Differentiation, v.26, no.10, pp 2139 - 2156
- Pages
- 18
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Cell Death and Differentiation
- Volume
- 26
- Number
- 10
- Start Page
- 2139
- End Page
- 2156
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1553
- DOI
- 10.1038/s41418-019-0282-0
- ISSN
- 1350-9047
1476-5403
- Abstract
- Most glioblastomas frequently recur at sites of radiotherapy, but it is unclear if changes in the tumor microenvironment due to radiotherapy influence glioblastoma recurrence. Here, we demonstrate that radiation-induced senescent glioblastoma cells exhibit a senescence-associated secretory phenotype that functions through NF kappa B signaling to influence changes in the tumor microenvironment, such as recruitment of Ly6G(+) inflammatory cells and vessel formation. In particular, Ly6G(+) cells promote conversion of glioblastoma cells to glioblastoma stem cells (GSCs) through the NOS2-NO-ID4 regulatory axis. Specific inhibition of NF kappa B signaling in irradiated glioma cells using the I kappa B alpha super repressor prevents changes in the tumor microenvironment and dedifferentiation of glioblastoma cells. Treatment with Ly6G-neutralizing antibodies also reduces the number of GSCs and prolongs survival in tumor-bearing mice after radiotherapy. Clinically, a positive correlation exists between Ly6G(+) cells and the NOS2-NO-ID4 regulatory axis in patients diagnosed with recurrent glioblastoma. Together, our results illustrate important roles for Ly6G(+) inflammatory cells recruited by radiation-induced SASP in cancer cell dedifferentiation and tumor recurrence.
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- Appears in
Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
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