Continued tumor growth after initial resection further complicates treatment

As discussed above, inclusion of RU-486 abolished Dex-mediated reactivation of FNMA and actin reorganization. We therefore asked whether RU-486 would block the effects of Dex on aggregate surface tension, cell motility, and DV. Inclusion of RU-486, 1) decreased Dex mediated cohesion to levels similar to untreated aggregates, 2) increased the motility of Dex treated GBM cells to levels similar to those treated with DMSO, and 3) blocked the effects of Dex on DV by effectively restoring DV to levels similar to those of carrier control treated aggregates. These results indicate that Dex, although having pleiotropic effects, specifically works through the GR pathway to suppress dispersal. Continued tumor growth after initial resection further complicates treatment efficacy for GBM. Release from contact inhibition of growth is a well-documented phenomenon in cancer. Various molecular mechanisms have been identified as potential regulators of this process, reviewed in. One of the more prevalent mechanisms involves loss of tumor cohesion, as a consequence of reduced E-cadherin expression or function. In GBM, N-cadherin Methyclothiazide predominates and it��s expression is not up regulated by Dex. However, Dex is able to increase cohesion by reactivating FNMA. We reasoned that an FNMA-dependent increase in cohesion could also reduce growth rate of GBM spheroids. To test this, it was first necessary to demonstrate that Dex did not have an effect on cell proliferation when cells were grown as sparsely plated 2D cultures. We then performed growth assays on 3Dspheroids in the absence and presence of Dex, and for one line, a combination of Dex andRU-486. On average, Dex treatment resulted ina4-fold decrease in growth rate. Since RU-486 effectively reduced aggregate cohesion to levels of untreated aggregates, we reasoned thatRU-486 should also block the effects of Dex on growth rate. This Mequinol proved to be the case since aggregates treated in a combination of Dex and RU-486 grew 6 times faster than those treated by Dex alone.Collectively, these results indicate that Dex not only has the capacity to decrease the detachment and dispersal of GBM tumor cells, but by increasing cohesion, may also function to reduce the growth rate of 3Dspheroids, at least invitro.