The DV assays performed here did not take into account changes that could influence DV by modulating strength of adhesion to substrate. However, previous Pidotimod studies have shown that strong-cell-cell cohesion can override strong cell-ECM adhesion, and prevent dispersal. In this study, we demonstrated that activating FNMA in primary GBM cells gave rise to a significant increase in the strength of cell-cell cohesion and reduced capacity for dispersal. We utilized a pharmacologic approach in gain-of-function assays in primary cells that were essentially FNMA deficient. Other studies employed loss of function assays using targeted short hairpin RNA to deplete fibronectininU87-MG cells. Those studies concluded that disrupting the fibronectin matrix enhanced persistent directional migration of single cells and compromised collective invasion of spheroids through a laminin-rich matrix. This is consistent with our results. However, as stated previously, glioma cell migration varies widely between cell lines and is highly dependent on the composition of the ECM. Accordingly, care must be exercised when Ibudilast drawing general conclusions from studies using a single cell line. Also, in our experience, U87-MGcellshaveavery low capacity for FNMA and can only be induced to assemble a matrix if groups of cells are subjected to high tensile forces, such as spheroids that are allowed to spread on a rigid matrix, or allowed to cluster near edges of tissue culture plates. Spheroids ofU87-MG grown in hanging drop culture and that are not under tensile stress or that are grown in conventional 2D culture do not typically assemble a matrix. To disperse, glioma cells must also be able to physically squeeze through pores created by astrocytes that are of smaller diameter than that of their nucleus. To do so, they must undergo shape change and nuclear deformation��processes that require dramatic changes in cytoskeletal organization and in cellular mechanics. We asked whether Dex treatment could also impede the dispersal of GBM cells through an astrocyte-seeded scaffold. Here too, single cell dispersal was significantly impeded by Dex. Whether Dex increased the stiffness of GBM cells to a point that discouraged their dispersal is currently being assessed.