Angiogenesis and Tumor Targeting Unit, San Raffaele Scientific Institute, Milan, Italy.
Clin Cancer Res. 2011 Aug 15;17(16):5226-32. doi: 10.1158/1078-0432.CCR-10-0171. Epub 2011 May 16.
Angiopoietin-2 (ANG2), a ligand of the TIE2 receptor, modulates endothelial cell biology and destabilizes blood vessels to facilitate angiogenesis. Recent reports have shown that ANG2 inhibition, for example, by monoclonal antibodies, peptibodies, or CovX-Bodies, may achieve substantial antiangiogenic and antitumor responses in a variety of mouse tumor models, including spontaneous MMTV-PyMT mammary and RIP1-Tag2 pancreatic islet adenocarcinomas. There is also evidence that targeting the ANG2/TIE2 signaling pathway may inhibit the functions of TIE2-expressing macrophages (TEM), a tumor-associated macrophage subset endowed with proangiogenic activity in mouse tumor models. The clinical opportunities afforded by simultaneously targeting the effects of ANG2 on tumor angiogenesis and the proangiogenic activity of TEMs are discussed.
血管生成素 2（ANG2）是 TIE2 受体的配体，调节内皮细胞生物学并破坏血管稳定性以促进血管生成。最近的报告表明，ANG2 抑制，例如通过单克隆抗体、肽体或 CovX 体，可以在多种小鼠肿瘤模型中实现显著的抗血管生成和抗肿瘤反应，包括自发的 MMTV-PyMT 乳腺和 RIP1-Tag2 胰腺胰岛腺癌。还有证据表明，靶向 ANG2/TIE2 信号通路可能抑制表达 TIE2 的巨噬细胞（TEM）的功能，TEM 是一种肿瘤相关巨噬细胞亚群，在小鼠肿瘤模型中具有促血管生成活性。同时靶向 ANG2 对肿瘤血管生成的影响和 TEM 的促血管生成活性的临床机会也进行了讨论。
