Regulatory effects of IL-1β in the interaction of GBM and tumor-associated monocyte through VCAM-1 and ICAM-1.

Glioblastoma (GBM) is the most common and lethal brain tumor with high inflammation. GBM cells infiltrate microglia and macrophages and are surrounded by pro-inflammatory cytokines. Interleukin (IL)-1β, which is abundantly expressed in the tumor microenvironment, is involved in tumor progression. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mediate cell-cell interactions, and these cell adhesion molecules (CAMs) can be regulated by cytokines in immune cells or cancer cells in the inflammatory tumor microenvironment. In this study, we found that ICAM-1 and VCAM-1 expression was induced when GBM cells were treated with IL-1β, and that adhesive interaction between monocytes and GBM cells increased accordingly. The levels of soluble CAMs (sICAM-1 and sVCAM-1) were also increased in the supernatants induced by IL-1β. Furthermore, the conditioned media contained sICAM-1 and sVCAM-1, which further promoted IL-6 and CCL2 expression in differentiated macrophages. IL-1β downregulated Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1) in GBM. The expression of ICAM-1 and VCAM-1 was regulated by p38, AKT, and NF-κB signaling pathways, which were modulated by SHP-1 signaling. The present study suggests that IL-1β-induced protein expression of ICAM-1 and VCAM-1 in GBM may modulate the adhesive interaction between GBM and monocytes. In addition, IL-1β also induced the soluble form of ICAM-1 and VCAM-1 in GBM, which plays a key role in the regulation of tumor-associated monocyte/macrophage polarization. Copyright © 2021 Elsevier B.V. All rights reserved.

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Ching-Kai Shen, Bor-Ren Huang, Wei-Lan Yeh, Chao-Wei Chen, Yu-Shu Liu, Sheng-Wei Lai, Wen-Pei Tseng, Dah-Yuu Lu, Cheng-Fang Tsai. Regulatory effects of IL-1β in the interaction of GBM and tumor-associated monocyte through VCAM-1 and ICAM-1. European journal of pharmacology. 2021 Aug 15;905:174216

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PMID: 34058204

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