纤维连接蛋白
整合素
运动性
细胞生物学
化学
粘附
调节器
基质(化学分析)
生物
基因
生物化学
细胞
细胞外基质
色谱法
有机化学
作者
Seon Yong Lee,Seung‐Chul Choi,Min Seok Lee,Amanzhol Kurmashev,Hae Nim Lee,Young Gyu Ko,Kanghun Lee,Soon‐Ki Jeong,Jihye Seong,Joo H. Kang,Hyunggee Kim
标识
DOI:10.1096/fj.202100452rr
摘要
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 .
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