Anti-PIGF inhibits growth of VEGF(R)-Inhibitor-Resistant tumors without affecting healthy vessels
Anti-PIGF inhibits growth of VEGF(R)-Inhibitor-Resistant tumors without affecting healthy vessels
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DOI：
10.1016/j.cell.2007.08.038
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发表时间：
2007-11-02
期刊：
影响因子：
64.5
通讯作者：
Carmeliet, Peter
中科院分区：
文献类型：
--
作者：
Fischer, Christian;Jonckx, Bart;Carmeliet, Peter
需要具有互补机制的新型抗血管生成策略来最大限度地提高有效性并减少对当前血管生成抑制剂的耐药性。我们探索了α - PIGF的治疗潜力和机制，α - PIGF是一种抗胎盘生长因子（PIGF）的抗体，是VEGF的同源物，在疾病中调节血管生成开关，而不是在健康中。α - PIGF抑制多种肿瘤的生长和转移，包括对VEGF(R)抑制剂（VEGF(R)Is）耐药的肿瘤（VEGF(R)Is），增强化疗和VEGF(R)Is的疗效。α - PIGF抑制血管生成、淋巴管生成和肿瘤细胞运动。与VEGF(R)Is不同，α - PIGF阻止了血管生成巨噬细胞的浸润和严重的肿瘤缺氧，因此，没有开启血管生成拯救程序，导致对VEGF(R)Is的抵抗。此外，它没有引起或增强VEGF(R) i相关的副作用。α - PIGF的有效性和安全性，其与VEGF(R)Is的多效性和互补机制，以及可忽略不计的血管生成拯救程序诱导，表明α - PIGF可能构成癌症治疗的新途径。
Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alpha PIGF, an antibody against placental growth factor (PIGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alpha PIGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alpha PIGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alpha PIGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alpha PIGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alpha PIGF may constitute a novel approach for cancer treatment.