Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells

Cells. 2020 Aug 21;9(9):1930. doi: 10.3390/cells9091930.

Abstract

The mesenchymal phenotype of glioblastoma multiforme (GBM), the most frequent and malignant brain tumor, is associated with the worst prognosis. The epithelial-mesenchymal transition (EMT) is a cell plasticity mechanism involved in GBM malignancy. In this study, we determined 17β-estradiol (E2)-induced EMT by changes in cell morphology, expression of EMT markers, and cell migration and invasion assays in human GBM-derived cell lines. E2 (10 nM) modified the shape and size of GBM cells due to a reorganization of actin filaments. We evaluated EMT markers expression by RT-qPCR, Western blot, and immunofluorescence.We found that E2 upregulated the expression of the mesenchymal markers, vimentin, and N-cadherin. Scratch and transwell assays showed that E2 increased migration and invasion of GBM cells. The estrogen receptor-α (ER-α)-selective agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 10 nM) affected similarly to E2 in terms of the expression of EMT markers and cell migration, and the treatment with the ER-α antagonist methyl-piperidino-pyrazole (MPP, 1 μM) blocked E2 and PPT effects. ER-β-selective agonist diarylpropionitrile (DNP, 10 nM) and antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazole[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 1 μM) showed no effects on EMT marker expression. These data suggest that E2 induces EMT activation through ER-α in human GBM-derived cells.

Keywords: 17β-estradiol (E2); epithelial–mesenchymal transition (EMT); estrogen receptors (ERs); glioblastoma multiforme (GBM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial-Mesenchymal Transition / drug effects*
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Estrogens / pharmacology
  • Estrogens / therapeutic use*
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans

Substances

  • Estrogens
  • Estradiol