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Proinvasive extracellular matrix remodeling in tumor microenvironment in response to radiation

 Ki-Chun Yoo  ;  Yongjoon Suh  ;  Yoojeong An  ;  Hae-June Lee  ;  Ye Ji Jeong  ;  Nizam Uddin  ;  Yan-Hong Cui  ;  Tae-Hoon Roh  ;  Jin-Kyoung Shim  ;  Jong Hee Chang  ;  Jong Bae Park  ;  Min-Jung Kim  ;  In-Gyu Kim  ;  Seok-Gu Kang  ;  Su-Jae Lee 
 ONCOGENE, Vol.37(24) : 3317-3328, 2018 
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Ionizing radiation is widely used for patient with glioblastoma (GBM). However, the effect of radiation on patient survival is marginal and upon recurrence tumors frequently shift toward mesenchymal subtype adopting invasiveness. Here, we show that ionizing radiation affects biomechanical tension in GBM microenvironment and provides proinvasive extracellular signaling cue, hyaluronic acid (HA)-rich condition. In response to radiation, HA production was increased in GBM cells by HA synthase-2 (HAS2) that was transcriptionally upregulated by NF-kB. Notably, NF-kB was persistently activated by IL-1alpha-feedback loop, making HA abundance in tumor microenvironment after radiation. Radiation-induced HA abundance causally has been linked to invasiveness of GBM cells by generating movement track as an extracellular matrix, and by acting as a signaling ligand for CD44 receptor, leading to SRC activation, which is sufficient for mesenchymal shift of GBM cells. Collectively, our findings provide an explanation for the frequent brain tumor relapse after radiotherapy, and potential therapeutic targets to block mesenchymal shift upon relapse.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Chang, Jong Hee(장종희)
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