Inhibition of CHI3L1 decreases N-cadherin and VCAM-1 levels in glioblastoma

抑制 CHI3L1 可降低胶质母细胞瘤中的 N-钙粘蛋白和 VCAM-1 水平

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作者:Agnieszka Rusak, Marlena Gąsior-Głogowska, Azzurra Sargenti, Edward Krzyżak, Krzysztof Kotowski, Monika Mrozowska, Tomasz Górnicki, Krzysztof Kujawa, Piotr Dzięgiel

Conclusion

Inhibition of CHI3L1 has the potential to reduce the invasiveness of GBM tumors. The 3D model of GBM spheroids is of great significance for investigating changes in membrane proteins and the tumor microenvironment.

Methods

We analyzed the interactions between CHI3L1 and the inhibitor G721-0282 in molecular docking and molecular dynamics (in silico) and infrared spectroscopy. Uptake of G721-0282 in GBM spheroids was measured using a label-free physical cytometer. Changes in E-, N- and VE-cadherins, VCAM-1, and EGFR were analyzed by immunohistochemical reactions, Western blot, and ddPCR methods in U-87 MG cells and GBM spheroids consisting of U-87 MG glioblastoma cells, HMEC-1 endothelial cells and macrophages;

Results

A direct interaction between CHI3L1 and G721-0282 was confirmed. G721-0282 decreased N-cadherins and VCAM-1 in GBM spheroids, but the changes in the 2D model of U-87 MG glioblastoma cells were different;

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