Broggini Thomas, Stange Lena, Lucia Kristin Elizabeth, Vajkoczy Peter, Czabanka Marcus
Department of Neurosurgery, University Hospital Frankfurt, 60528 Frankfurt am Main, Germany.
Department of Neurosurgery, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Life (Basel). 2022 May 6;12(5):691. doi: 10.3390/life12050691.
Vascular guidance is critical in developmental vasculogenesis and pathological angiogenesis. Brain tumors are strongly vascularized, and antiangiogenic therapy was anticipated to exhibit a strong anti-tumor effect in this tumor type. However, vascular endothelial growth factor A (VEGFA) specific inhibition had no significant impact in clinical practice of gliomas. More research is needed to understand the failure of this therapeutic approach. EphrinB2 has been found to directly interact with vascular endothelial growth factor receptor 2 (VEGFR2) and regulate its activity. Here we analyzed the expression of ephrinB2 and EphB4 in human glioma, we observed vascular localization of ephrinB2 in physiology and pathology and found a significant survival reduction in patients with elevated ephrinB2 tumor expression. Induced endothelial specific depletion of ephrinB2 in the adult mouse () had no effect on the quiescent vascular system of the brain. However, we found glioma growth and perfusion altered in animals similar to the effects observed with antiangiogenic therapy. No additional anti-tumor effect was observed in animals treated with antiangiogenic therapy. Our data indicate that ephrinB2 and VEGFR2 converge on the same pathway and intervention with either molecule results in a reduction in angiogenesis.
血管导向在发育性血管生成和病理性血管生成中至关重要。脑肿瘤血管丰富，抗血管生成疗法预期对这种肿瘤类型具有强大的抗肿瘤作用。然而，血管内皮生长因子A（VEGFA）特异性抑制在胶质瘤的临床实践中并无显著影响。需要更多研究来理解这种治疗方法失败的原因。已发现 EphrinB2 可直接与血管内皮生长因子受体 2（VEGFR2）相互作用并调节其活性。在此，我们分析了 EphrinB2 和 EphB4 在人类胶质瘤中的表达，观察到 EphrinB2 在生理和病理状态下的血管定位，并发现 EphrinB2 肿瘤表达升高的患者生存率显著降低。在成年小鼠中诱导内皮细胞特异性缺失 EphrinB2 对大脑的静止血管系统没有影响。然而，我们发现 EphrinB2 缺失的动物中胶质瘤生长和灌注发生改变，类似于抗血管生成疗法所观察到的效果。在用抗血管生成疗法治疗的 EphrinB2 缺失动物中未观察到额外的抗肿瘤作用。我们的数据表明，EphrinB2 和 VEGFR2 汇聚于同一条通路，对任一分子进行干预都会导致血管生成减少。
