Dataset Information

Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells.

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 17?-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-? (ER-?)-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-? antagonist methyl-piperidino-pyrazole (MPP, 1 ?M) blocked E2 and PPT effects. ER-?-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 ?M) showed no effects on EMT marker expression. These data suggest that E2 induces EMT activation through ER-? in human GBM-derived cells.

SUBMITTER: Hernandez-Vega AM

PROVIDER: S-EPMC7564468 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells.

Hernández-Vega Ana M AM Del Moral-Morales Aylin A Zamora-Sánchez Carmen J CJ Piña-Medina Ana G AG González-Arenas Aliesha A Camacho-Arroyo Ignacio I

Cells 20200821 9

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 r ...[more]

PMID: 32825553

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Project description:We propose the hypothesis that loss of estrogen receptor function which leads to endocrine resistance in breast cancer, also results in trans-differentiation from an epithelial to a mesenchymal phenotype that is responsible for increased aggressiveness and metastatic propensity. siRNA mediated silencing of the estrogen receptor in MCF7 breast cancer cells resulted in estrogen/tamoxifen resistant cells (pII) with altered morphology, increased motility with rearrangement and switch from a keratin/actin to a vimentin based cytoskeleton, and ability to invade simulated components of the extracellular matrix. Phenotypic profiling using an Affymetrix Human Genome U133 plus 2.0 GeneChip indicated geometric fold changes ≥ 3 in approximately 2500 identifiable unique sequences, with about 1270 of these being up-regulated in pII cells. Changes were associated with genes whose products are involved in cell motility, loss of cellular adhesion and interaction with the extracellular matrix. Selective analysis of the data also showed a shift from luminal to basal cell markers and increased expression of a wide spectrum of genes normally associated with mesenchymal characteristics, with consequent loss of epithelial specific markers. Over-expression of several peptide growth factors and their receptors are indicative of an increased contribution to the higher proliferative rates of pII cells as well as aiding their potential for metastatic activity. Signalling molecules that have been identified as key transcriptional drivers of epithelial to mesenchymal transition were also found to be elevated in pII cells. These data support our hypothesis that induced loss of estrogen receptor in previously estrogen/antiestrogen sensitive cells is a trigger for the concomitant loss of endocrine dependence and onset of a series of possibly parallel events that changes the cell from an epithelial to a mesenchymal type. Inhibition of this transition through targeting of specific mediators may offer a useful supplementary strategy to circumvent the effects of loss of endocrine sensitivity.

Dataset Information

Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells.

Publications

Estradiol Induces Epithelial to Mesenchymal Transition of Human Glioblastoma Cells.

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