Shibuya Masabumi
Department of Molecular Oncology, Tokyo Medical and Dental University, Japan.
FEBS J. 2009 Sep;276(17):4636-43. doi: 10.1111/j.1742-4658.2009.07175.x. Epub 2009 Jul 31.
The angiogenic process in the central nervous system (CNS) is basically regulated by typical angiogenic signaling systems such as vascular endothelial growth factor (VEGF)-VEGF receptors and angiopoietin-Tie receptors. In addition to regular endothelial-pericyte interaction, the CNS vasculature has a unique system of cell to cell communication between endothelial cells and astrocytes which is known as the blood-brain barrier. Among the pathological conditions of the CNS vascular network, stroke is a major disease in which the supply of blood is decreased. Pro-angiogenic therapy using natural VEGF-A has so far been unsuccessful, indicating the possible need for a new approach related to upstream or downstream regulators involved in the VEGF-signaling pathway, or alternate VEGF family members. By contrast, a pathological increase in the blood supply in the CNS is seen in brain tumors, in particular malignant gliomas. In phase II clinical trials, anti-VEGF therapies have been shown to suppress tumor growth and improve survival rates to some extent. However, tumor invasion and the distant metastasis of gliomas can occur following anti-angiogenic therapy. Further studies are needed to obtain safer clinical outcomes by developing new strategies with combination therapy using known anti-angiogenic drugs or by developing unique medicines specifically targeting the blood vessels in brain tumors.
中枢神经系统（CNS）中的血管生成过程基本上由典型的血管生成信号系统调节，如血管内皮生长因子（VEGF）-VEGF受体和血管生成素-Tie受体。除了常规的内皮细胞-周细胞相互作用外，CNS脉管系统在内皮细胞和星形胶质细胞之间还有一种独特的细胞间通讯系统，即血脑屏障。在CNS血管网络的病理状况中，中风是一种血液供应减少的主要疾病。迄今为止，使用天然VEGF-A的促血管生成疗法尚未成功，这表明可能需要一种与VEGF信号通路中上游或下游调节因子相关的新方法，或替代VEGF家族成员。相比之下，CNS血液供应的病理性增加见于脑肿瘤，尤其是恶性胶质瘤。在II期临床试验中，抗VEGF疗法已被证明在一定程度上可抑制肿瘤生长并提高生存率。然而，抗血管生成治疗后胶质瘤可能会发生肿瘤侵袭和远处转移。需要进一步研究，通过开发使用已知抗血管生成药物的联合治疗新策略或开发专门针对脑肿瘤血管的独特药物，以获得更安全的临床结果。
