Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth
Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth
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DOI：
10.1158/0008-5472.can-04-4012
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发表时间：
2005-07-01
期刊：
影响因子：
11.2
通讯作者：
Aurrand-Lions, M
中科院分区：
文献类型：
--
作者：
Lamagna, C;Hodivala-Dilke, KM;Aurrand-Lions, M
交界性黏附分子-C(JAM-C)是一种定位于内皮细胞间接触的黏附分子，参与白细胞的跨内皮细胞迁移。JAM-C蛋白与极性复杂分子相互作用，调节小GTP酶CDC42的活性。血管生成过程涉及内皮连接的重排，并涉及细胞极性的调节。我们利用肿瘤移植物和缺氧诱导的视网膜新生血管来测试JAM-C是否在血管生成中发挥作用。用针对JAM-C的单抗治疗可减少肿瘤生长和巨噬细胞向肿瘤的渗透。该抗体在体内减少了低氧诱导的视网膜新生血管模型中的血管生成，并在体外减少了主动脉环血管的生长。重要的是，该抗体在体内不会引起病理性副作用。这些发现首次显示了JAM-C在血管生成中的作用，并将JAM-C确定为抗肿瘤治疗的有价值的靶点。
The junctional adhesion molecule-C (JAM-C) was recently described as an adhesion molecule localized at interendothelial contacts and involved in leukocyte transendothelial migration. The protein JAM-C interacts with polarity complex molecules and regulates the activity of the small GTPase Cdc42. The angiogenesis process involves rearrangement of endothelial junctions and implicates modulation of cell polarity. We tested whether JAM-C plays a role in angiogenesis using tumor grafts and hypoxia-induced retinal neovascularization. Treatment with a monoclonal antibody directed against JAM-C reduces tumor growth and infiltration of macrophages into tumors. The antibody decreases angiogenesis in the model of hypoxia-induced retinal neovascularization in vivo and vessel outgrowth from aortic rings in vitro. Importantly, the antibody does not induce pathologic side effects in vivo. These findings show for the first time a role for JAM-C in angiogenesis and define JAM-C as a valuable target for antitumor therapies.