Department of Experimental Neurosurgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Int J Mol Sci. 2021 Mar 5;22(5):2634. doi: 10.3390/ijms22052634.
We aimed to evaluate the angiogenic capacity of CXCL2 and IL8 affecting human endothelial cells to clarify their potential role in glioblastoma (GBM) angiogenesis. Human GBM samples and controls were stained for proangiogenic factors. Survival curves and molecule correlations were obtained from the TCGA (The Cancer Genome Atlas) database. Moreover, proliferative, migratory and angiogenic activity of peripheral (HUVEC) and brain specific (HBMEC) primary human endothelial cells were investigated including blockage of CXCR2 signaling with SB225502. Gene expression analyses of angiogenic molecules from endothelial cells were performed. Overexpression of VEGF and CXCL2 was observed in GBM patients and associated with a survival disadvantage. Molecules of the pathway correlated but no relation for and was found. Interestingly, receptors of endothelial cells were not induced by addition of proangiogenic factors in vitro. Proliferation and migration of HUVEC were increased by VEGF, CXCL2 as well as IL8. Their sprouting was enhanced through VEGF and CXCL2, while IL8 showed no effect. In contrast, brain endothelial cells reacted to all proangiogenic molecules. Additionally, treatment with a CXCR2 antagonist led to reduced chemokinesis and sprouting of endothelial cells. We demonstrate the impact of CXCR2 signaling on endothelial cells supporting an impact of this pathway in angiogenesis of glioblastoma.
我们旨在评估 CXCL2 和 IL8 对人内皮细胞的血管生成能力，以阐明它们在胶质母细胞瘤 (GBM) 血管生成中的潜在作用。对人 GBM 样本和对照进行了促血管生成因子染色。从 TCGA（癌症基因组图谱）数据库中获得了生存曲线和分子相关性。此外，还研究了外周（HUVEC）和脑特异（HBMEC）原代人内皮细胞的增殖、迁移和血管生成活性，包括用 SB225502 阻断 CXCR2 信号。对内皮细胞的血管生成分子进行了基因表达分析。在 GBM 患者中观察到 VEGF 和 CXCL2 的过表达，并与生存劣势相关。 通路的分子相关，但 和 之间没有关系。有趣的是，内皮细胞的受体在体外添加促血管生成因子时没有被诱导。VEGF、CXCL2 和 IL8 均可增加 HUVEC 的增殖和迁移。它们的发芽通过 VEGF 和 CXCL2 增强，而 IL8 则没有影响。相比之下，脑内皮细胞对所有促血管生成分子都有反应。此外，用 CXCR2 拮抗剂治疗可导致趋化性和内皮细胞发芽减少。我们证明了 CXCR2 信号对内皮细胞的影响，支持该途径在胶质母细胞瘤血管生成中的作用。
