Among the deadliest human cancers is glioblastoma (GBM) for which new treatment approaches are urgently needed. Here, the effects of the cyclic decapeptide, uPAcyclin, are investigated using the U87-MG, U251-MG, and U138-MG human GBM and C6 rat cell models. All GBM cells express the αV-integrin subunit, the target of uPAcyclin, and bind specifically to nanomolar concentrations of the decapeptide. Although peptide exposure affects neither viability nor cell proliferation rate, nanomolar concentrations of uPAcyclin markedly inhibit the directional migration and matrix invasion of all GBM cells, in a concentration- and αV-dependent manner. Moreover, wound healing rate closure of U87-MG and C6 rat glioma cells is reduced by 50% and time-lapse videomicroscopy studies show that the formation of vascular-like structures by U87-MG in three-dimensional matrix cultures is markedly inhibited by uPAcyclin. A strong reduction in the branching point numbers of the U87-MG, C6, and U251-MG cell lines undergoing vasculogenic mimicry, in the presence of nanomolar peptide concentrations, was observed. Lysates from matrix-recovered uPAcyclin-exposed cells exhibit a reduced expression of VE-cadherin, a prominent factor in the acquisition of vascular-like structures. In conclusion, these results indicate that uPAcyclin is a promising candidate to counteract the formation of new vessels in novel targeted anti-GBM therapies.
胶质母细胞瘤（GBM）是最致命的人类癌症之一，亟需新的治疗方法。本研究采用U87-MG、U251-MG、U138-MG人源GBM细胞及C6大鼠细胞模型，探究环状十肽uPAcyclin的作用机制。所有GBM细胞均表达uPAcyclin的作用靶点αV整合素亚基，并能特异性结合纳摩尔浓度水平的该十肽。虽然肽暴露不影响细胞活力与增殖速率，但纳摩尔浓度的uPAcyclin能以浓度依赖和αV依赖的方式显著抑制所有GBM细胞的定向迁移与基质侵袭能力。此外，U87-MG和C6大鼠胶质瘤细胞的伤口愈合速率降低50%，延时视频显微技术显示uPAcyclin能显著抑制U87-MG细胞在三维基质培养中形成血管样结构。在纳摩尔浓度肽存在条件下，观察到U87-MG、C6及U251-MG细胞系在血管生成拟态过程中的分支点数量大幅减少。从基质中回收的uPAcyclin处理细胞裂解液显示，血管样结构形成关键因子VE-钙黏蛋白表达量下降。综上所述，这些结果表明uPAcyclin在新型靶向抗GBM治疗中具有抑制新生血管形成的潜力。
肿瘤(癌症)患者之家