Glioma cell dispersion is driven by alpha 5 integrin-mediated cell-matrix and cell-cell interactions

摘要

Glioblastoma multiform (GBM) is the most common and most aggressive primary brain tumor. The fibronectin receptor, alpha 5 integrin is a pertinent novel therapeutic target. Despite numerous data showing that alpha 5 integrin support tumor cell migration and invasion, it has been reported that alpha 5 integrin can also limit cell dispersion by increasing cell-cell interaction. In this study, we showed that alpha 5 integrin was involved in cell-cell interaction and gliomasphere formation. alpha 5-mediated cell-cell cohesion limited cell dispersion from spheroids in fibronectin-poor microenvironment. However, in fibronectin-rich microenvironment, alpha 5 integrin promoted cell dispersion. Ligand-occupied alpha 5 integrin and fibronectin were distributed in fibril-like pattern at cell-cell junction of evading cells, forming cell-cell fibrillar adhesions. Activated focal adhesion kinase was not present in these adhesions but was progressively relocalized with alpha 5 integrin as cell migrates away from the spheroids. alpha 5 integrin function in GBM appears to be more complex than previously suspected. As GBM overexpressed fibronectin, it is most likely that in vivo, alpha 5-mediated dissemination from the tumor mass overrides alpha 5-mediated tumor cell cohesion. In this respect, alpha 5-integrin antagonists may be useful to limit GBM invasion in brain parenchyma. (C) 2016 Elsevier Ireland Ltd. All rights reserved.