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

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Abstract

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-1α-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.

Original languageEnglish
Pages (from-to)3317-3328
Number of pages12
JournalOncogene
Volume37
Issue number24
DOIs
Publication statusPublished - 2018 Jun 1

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yoo, K. C., Suh, Y., An, Y., Lee, H. J., Jeong, Y. J., Uddin, N., Cui, Y. H., Roh, T. H., Shim, J. K., Chang, J. H., Park, J. B., Kim, M. J., Kim, I. G., Kang, S. G., & Lee, S. J. (2018). Proinvasive extracellular matrix remodeling in tumor microenvironment in response to radiation. Oncogene, 37(24), 3317-3328. https://doi.org/10.1038/s41388-018-0199-y