Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the ECM-related genes were highly expressed in the cells within the PVN where fibronectin (FN) induced RF formation. By disrupting candidates of FN-binding integrins, integrin α5β1 was identified as the main regulator of RF formation. De novo RFs were produced at the trailing edge, and focal adhesions were actively localized in RFs, indicating that adhesive force makes RFs remain at the bottom surface. Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5β1 interaction and promoted their motility .

中文翻译：

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纤连蛋白-整合素α5β1相互作用产生的收缩纤维促进脑肿瘤细胞的运动

胶质母细胞瘤（GBM）是一种具有高度浸润性特征的难治性疾病。在过去十年中，GBM 血管周围生态位 (PVN) 被描述为传播途径。在这里，我们研究了拖曳的膜结构，即收缩纤维 (RF)，是由血管周围细胞外基质 (ECM) 蛋白形成的。通过使用解剖学 GBM 数据库，我们验证了 ECM 相关基因在 PVN 内的细胞中高度表达，其中纤连蛋白 (FN) 诱导 RF 形成。通过破坏 FN 结合整合素的候选物，整合素 α5β1 被确定为 RF 形成的主要调节因子。在后缘处产生了从头 RFs，并且在 RFs 中活跃地定位了粘着斑，表明粘附力使 RFs 保留在底面。此外，我们观察到，与没有 RFs 的通道中相比，GBM 细胞更频繁地沿着微流体通道中由先前细胞形成的残余 RFs 迁移，这表明 GBM 的浸润特征可归因于由先前细胞形成的 RFs 与化学引诱线索一致. 总之，我们证明了 GBM 细胞脱落的膜结构是由 FN-整合素 α5β1 相互作用维持的，并促进了它们的运动。