Despite aggressive clinical treatment, recurrence of glioblastoma multiforme (GBM) is unavoidable, and the clinical outcome is still poor. A convincing explanation is the phenotypic transition of GBM cells upon aggressive treatment such as radiotherapy. However, the microenvironmental factors contributing to GBM recurrence after treatment remain unexplored. Here, it is shown that radiation-treated GBM cells produce soluble intercellular adhesion molecule-1 (sICAM-1) which stimulates the infiltration of macrophages, consequently enriching the tumor microenvironment with inflammatory macrophages. Acting as a paracrine factor, tumor-derived sICAM-1 induces macrophages to secrete wingless-type MMTV integration site family, member 3A (WNT3A), which promotes a mesenchymal shift of GBM cells. In addition, blockade of either sICAM-1 or WNT3A diminishes the harmful effect of radiation on tumor progression. Collectively, the findings indicate that cellular crosstalk between GBM and macrophage through sICAM-1-WNT3A oncogenic route is involved in the mesenchymal shift of GBM cells after radiation, and suggest that radiotherapy combined with sICAM-1 targeted inhibition would improve the clinical outcome of GBM patients.
|Publication status||Published - 2022 Jan 14|
Bibliographical noteFunding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2019M3E5D1A01069361, 2019R1A2C2087551, and 2019R1A2C3004155).
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Chemical Engineering(all)
- Materials Science(all)
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Physics and Astronomy(all)