Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor due to its invasive phenotype. Ras suppressor 1 (RSU-1) is a cell-extracellular matrix adhesion protein and we recently found that it promotes cell invasion in aggressive cells and inhibits it in non-invasive. Growth differentiation factor-15 (GDF15) is known to be involved in actin cytoskeleton reorganization and metastasis. In this study, we used three brain cell lines (H4, SW1088 and A172) with increasing RSU-1 expression levels and invasive capacity and decreasing GDF15 levels to investigate the interplay between RSU-1 and GDF15 with regard to cell invasion. Four experimental approaches were used: (a) GDF15 treatment, (b) Rsu-1 silencing, (c) GDF15 silencing, and (d) combined GDF15 treatment and RSU-1 silencing. We found that the differential expression of RSU-1 and GDF15 in H4 and A172 cells leading to inhibition of cell invasion in H4 cells and promotion in A172 through respective changes in PINCH1, RhoA and MMP-13 expression. Interestingly SW1088, with intermediate RSU-1 and GDF15 expression, were not affected by any treatment. We conclude that there is a strong connection between RSU-1 and GDF15 in H4, SW1088 and A172 cells and the relative expression of these two proteins is fundamental in affecting their invasive fate.