Activation of membrane progesterone receptor-alpha increases proliferation, migration, and invasion of human glioblastoma cells.

Abstract

Glioblastoma is the most frequent and aggressive brain tumor due to its high capacity to migrate and invade normal brain tissue. The steroid hormone progesterone (P4) contributes to the progression of glioblastoma by promoting proliferation, migration, and cellular invasion through the activation of its intracellular receptor (PR). However, the use of PR antagonist RU486 partially blocks the effects of P4, suggesting the participation of signaling pathways such as those mediated by membrane receptors to P4 (mPRs). Therefore, this study aimed to investigate the effects of mPRα subtype activation on proliferation, migration, and invasion of human glioblastoma cells. We treated human glioblastoma cell lines U87 and U251 with the specific mPRα agonist Org OD 02-0, and evaluated its effects on cell number, proliferation, migration, and invasion. Additionally, we measured the phosphorylation of the kinases Src and Akt in both cell lines upon Org OD 02-0 treatment. Org OD 02-0 (100 nM) augmented the number of U87 and U251 cells by increasing cell proliferation. The treatment with this agonist also increased U87 and U251 cell migration and invasion. Both proliferation and cell invasion decreased when mPRα expression was silenced. Finally, we observed that Org OD 02-0 increased the content of p-Src and p-Akt in both cell lines. Our data suggest that P4 produces its effects in human glioblastoma progression not only by PR interaction but also through cell signaling pathways activated by mPRα.