Melanoma, a form of skin cancer, is one of the most common cancers in young men and women. Tumors require angiogenesis to provide oxygen and nutrients for growth. Pro-angiogenic molecules such as VEGF and anti-angiogenic molecules such as sFlt-1 control angiogenesis. In addition, the serum protein, Beta2 Glycoprotein I (β2-GPI) induces or inhibits angiogenesis depending on conformation and concentration. β2-GPI binds to proteins and negatively charged phospholipids on hypoxic endothelial cells present in the tumor microenvironment. We hypothesized that peptides derived from the binding domain of β2-GPI would regulate angiogenesis and melanoma growth. In vitro analyses determined the peptides reduced endothelial cell migration and sFlt-1 secretion. In a syngeneic, immunocompetent mouse melanoma model, β2-GPI-derived peptides also reduced melanoma growth in a dose-dependent response with increased sFlt-1 and attenuated vascular markers compared to negative controls. Importantly, administration of peptide with sFlt-1 antibody resulted in tumor growth. These data demonstrate the therapeutic potential of novel β2-GPI-derived peptides to attenuate tumor growth and endothelial migration is sFlt-1 dependent.

黑色素瘤是皮肤癌的一种形式，是年轻男性和女性中最常见的癌症之一。肿瘤需要血管生成来提供生长所需的氧气和营养。促血管生成分子（例如 VEGF）和抗血管生成分子（例如 sFlt-1）控制血管生成。此外，血清蛋白 Beta2 糖蛋白 I (β2-GPI) 根据构象和浓度诱导或抑制血管生成。β2-GPI 与肿瘤微环境中缺氧内皮细胞上的蛋白质和带负电的磷脂结合。我们假设源自 β2-GPI 结合域的肽可以调节血管生成和黑色素瘤生长。体外分析确定这些肽减少了内皮细胞迁移和 sFlt-1 分泌。在同基因、免疫功能正常的小鼠黑色素瘤模型中，与阴性对照相比，β2-GPI 衍生肽还以剂量依赖性反应减少了黑色素瘤的生长，并增加了 sFlt-1 并减弱了血管标志物。重要的是，将肽与 sFlt-1 抗体一起施用会导致肿瘤生长。这些数据证明新型 β2-GPI 衍生肽减弱肿瘤生长和内皮迁移的治疗潜力依赖于 sFlt-1。