Functionally relevant markers of glioblastoma stem-like cells (GSCs) have potential for therapeutic targeting to treat this aggressive disease. Here we used generation and screening of thousands of monoclonal antibodies to search for receptors and signaling pathways preferentially enriched in GSCs. We identified integrin α7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses showed that ITGA7 plays a key functional role in growth and invasiveness of GSCs. We also found that targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. Our data, therefore, highlight ITGA7 as a glioblastoma biomarker and candidate therapeutic target.

中文翻译：

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整合素α7是胶质母细胞瘤的功能标记物和潜在的治疗靶标

胶质母细胞瘤干样细胞（GSC）的功能相关标记物具有潜在的治疗靶向性，可以治疗这种侵袭性疾病。在这里，我们使用了成千上万的单克隆抗体的产生和筛选来寻找优先富含GSC的受体和信号通路。我们发现整联蛋白α7（ITGA7）是GSC和主要的高级神经胶质瘤标本中的主要层粘连蛋白受体。综合数据集中的mRNA谱分析显示，高ITGA7表达与低度和高度神经胶质瘤患者的生存呈负相关。体外和体内分析表明，ITGA7在GSC的生长和侵袭性中起着关键的功能作用。我们还发现RNAi靶向ITGA7或阻断mAb会破坏层粘连蛋白诱导的信号传导，并且导致了肿瘤植入的显着延迟，以及肿瘤大小和侵袭的强烈减少。因此，我们的数据突出了ITGA7作为胶质母细胞瘤的生物标志物和候选治疗靶标。