Abstract
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.
Highlights
(GBM) is unavoidable, and the clinical outcome is still poor
The findings indicate that cellular tein belonging to the immunoglobulin crosstalk between glioblastoma multiforme (GBM) and macrophage through soluble ICAM-1 (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
Using the Rembrandt database, patients with high expression of Intercellular adhesion molecule-1 (ICAM-1) showed shorter survival than the rest of the patients (Figure 5G). These results suggest that sICAM-1, which is elevated upon radiation, acts as a chemoattractant that entices macrophages into tumor-microenvironment and stimulates these macrophages to secrete WNT3A, which in turn induces the transition of GBM into the mesenchymal state (Figure 5H)
Summary
(GBM) is unavoidable, and the clinical outcome is still poor. A convincing only 15 months.[1]. It is shown that radiation-treated GBM cells produce soluble intercellular adhesion mesenchymal-type exhibited greater invasiveness and worse prognosis compared to the other subtypes.[2] several strong lines of evidence suggest that molecule-1 (sICAM-1) which stimulates the infiltration of macrophages, radiation induces a mesenchymal shift of enriching the tumor microenvironment with inflammatory. 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. The findings indicate that cellular tein belonging to the immunoglobulin 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. Recurrence is tumor-educated macrophages produce wingless-type MMTV
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