出芽式肿瘤血管生成的分子调控机制

Molecular regulation mechanism of tumor sprouting angiogenesis

出芽式血管生成是肿瘤血管生成主要方式,其中出芽过程受到多种信号通路和相关分子的调控。新的研究发现,血管内皮细胞除了受VEGF/VEGFR-2诱导转化为尖端细胞出芽外,VEGFR-3也会高表达于肿瘤血管内皮,对尖端细胞的选择以及肿瘤血管分支进行双向调控。该文重点阐述了VEGF/VEGFR与Dll4/Notch1信号通路的平衡对肿瘤血管出芽的重要意义,同时Ang/Tie、HIF、整合素等信号与VEGF/VEGFRs信号相互作用也对肿瘤血管出芽进行调控。靶向针对于出芽式肿瘤血管初始出芽阶段的抗血管治疗策略是抑制肿瘤血管生成的新的着眼点。

Sprouting angiogenesis is the primary way of tumor an- giogenesis. The diverse pathways and molecules have been in- volved in angiogenesis, the tormation of new blood vessels. VEGF-A/VEGFR-2 has recently emerged as a key signal axis of angiogenesis. Moreover, VEGFR-3 which is highly expressed in the tumor vascular endothelial, plays a bimodal role in regulating angiogenesis by effectively controlling the number of vessel bran- ches and endothelial sprouts. The balance of VEGF/VEGFR andDll4/Notehl signaling pathways is significant in the sprouting an- giogenesis. The process of sprouting has been regulated by the in- tersection of VEGF/VEGFR signaling with other pathways, in- cluding angiopoieti/Tie, hypoxia-inducible factor, and integrin pathways. Thus, focuse on the initial stage of sprouting will be effective strategies for tumor anti-angiogenesis.