Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells

Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P-4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium. However, the role of P-4 in migration and invasion of astrocytoma cells as well as its effects on astrocytomas cytoskeleton remodeling is not known. In this work we evaluated these aspects in D54 and U251 cells derived from human astrocytomas from the highest degree of malignancy (grade IV, glioblastoma). Our results showed that in scratch-wound assays P-4 increased the number of D54 and U251 cells migrating from 3 to 48 h. Both RU486, a P-4 receptor (PR) antagonist, and an oligonucleotide antisense against PR significantly blocked P-4 effects. Transwell assays showed that P-4 significantly increased the number of invasive cells at 24 h. As in the case of migration, this effect was blocked by RU486. Finally, by Western blotting, an increase in the cofilin/p-cofilin ratio at 15 and 30 min and a decrease at 30 and 60 min in U251 and D54 cells, respectively, was observed after P-4, P-4 + RU486 and RU486 treatments. These data suggest that P-4 increases human astrocytoma cells migration and invasion through its intracellular receptor, and that cofilin activation by P-4 is independent of PR action. (C) 2015 Elsevier Inc. All rights reserved.