Dataset Information

Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues.

ABSTRACT: In the development of human cell-based assays, 3-dimensional (3D) cell culture models are intriguing as they are able to bridge the gap between animal models and traditional two-dimensional (2D) cell culture. Previous work has demonstrated that MCF-7 human breast carcinoma cells cultured in a 3D scaffold-free culture system self-assemble and develop into differentiated microtissues that possess a luminal space. Exposure to estradiol for 7 days decreased lumen formation in MCF-7 microtissues, altered microtissue morphology and altered expression of genes involved in estrogen signaling, cell adhesion and cell cycle regulation. Exposure to receptor-specific agonists for estrogen receptor alpha, estrogen receptor beta and g-protein coupled estrogen receptor resulted in unique, receptor-specific phenotypes and gene expression signatures. The use of a differentiated scaffold-free 3D culture system offers a unique opportunity to study the phenotypic and molecular changes associated with exposure to estrogenic compounds.

SUBMITTER: Vantangoli MM

PROVIDER: S-EPMC4803074 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues.

Vantangoli Marguerite M MM Wilson Shelby S Madnick Samantha J SJ Huse Susan M SM Boekelheide Kim K

Toxicology letters 20160224

In the development of human cell-based assays, 3-dimensional (3D) cell culture models are intriguing as they are able to bridge the gap between animal models and traditional two-dimensional (2D) cell culture. Previous work has demonstrated that MCF-7 human breast carcinoma cells cultured in a 3D scaffold-free culture system self-assemble and develop into differentiated microtissues that possess a luminal space. Exposure to estradiol for 7 days decreased lumen formation in MCF-7 microtissues, alt ...[more]

PMID: 26921789

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Project description:The fluorescence-based multi-analyte chip platform for the analysis of estrogenic and anti-estrogenic substances is a new in vitro tool for the high throughput screening of environmental samples. In contrast to existing tools, the chip investigates the complex action of xenoestrogens in a human cell model by characterizing protein expression. It allows for the quantification of 10 proteins secreted by MCF-7 cells, representing various biological and pathological endpoints of endocrine action and distinguishing between estrogen- and anti-estrogen-dependent secretion of proteins. Distinct protein secretion patterns of the cancer cell line after exposure to known estrogen receptor agonists ß-estradiol, bisphenol A, genistein, and nonylphenol as well as antagonists fulvestrant and tamoxifen demonstrate the potential of the chip. Stimulation of cells with Interleukin-1ß shifts concentrations of low abundant biomarkers towards the working range of the chip. In the non-stimulated cell culture, Matrix Metalloproteinase 9 (MMP-9) and Vascular Endothelial Growth Factor (VEGF) show differences upon treatment with antagonists and agonists of the estrogen receptor. In stimulated MCF-7 cells challenged with receptor agonists secretion of Monocyte Chemoattractant Protein (MCP-1), Interleukin-6 (IL-6), Rantes, and Interleukin-8 (IL-8) significantly decreases. In parallel, the proliferating effect of endocrine-disrupting substances in MCF-7 cells is assessed in a proliferation assay based on resazurin. Using ethanol as a solvent for test substances increases the background of proliferation and secretion experiments, while using dimethyl sulfoxide (DMSO) does not show any adverse effects. The role of the selected biomarkers in different physiological processes such as cell development, reproduction, cancer, and metabolic syndrome makes the chip an excellent tool for either indicating endocrine-disrupting effects in food and environmental samples, or for screening the effect of xenoestrogens on a cellular and molecular level.

Project description:There is increasing evidence showing that chronic non-bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor ? (ER?) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ER?-activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation.Male Sprague-Dawley rats (8 weeks, n?=?15) were divided into three groups: sham-saline group (n?=?5), formalin-vehicle group (n?=?5), and formalin-treatment group (n?=?5). The sham-saline group had sham operation and 50??l normal saline injected into each ventral lobe of the prostate. The formalin-vehicle group had 50??l 5% formalin injection into bilateral ventral lobes of the prostate. The formalin-treatment group was treated with 3?-Adiol (a selective ER? agonist precursor) at a dose of 3?mg/kg daily from 2 days before induction of prostatic inflammation, whereas formalin-vehicle rats received vehicle (olive oil). In each group, conscious cystometry was performed on day 28 after intraprostatic formalin injection or sham treatment. After cystometry, the bladder and prostate were harvested for evaluation of mRNA expression and histological analysis.In cystometric investigation, the mean number of non-voiding contractions was significantly greater and voiding intervals were significantly shorter in formalin-vehicle rats than those in sham-saline rats (P?<?0.05). In RT-qPCR analysis, mRNA expression of NGF, P2X2, and TRPA1 receptors was significantly increased in the bladder mucosa, and mRNA expression of TNF-?, iNOS and COX2 in the ventral lobes of prostate was significantly increased in formalin-vehicle rats compared with sham-saline rats (P?<?0.05). In addition, relative mRNA expression ratio of ER? to ER? (ER?/ER?) in the ventral lobes of prostate was significantly decreased in formalin-vehicle rats compared with sham-saline rats (P?<?0.05). These changes were ameliorated by 3?-Adiol administration in formalin-treatment rats.These results indicate that ER? activation by 3?-Adiol administration, which normalized the ER?/ER? expression ratio in the prostate, can improve not only prostatic inflammation, but also bladder overactivity. Therefore, ER? agonists might be useful for treating irritative bladder symptoms in patients with symptomatic BPH associated with prostatic inflammation. Prostate 77:803-811, 2017. © 2017 Wiley Periodicals, Inc.

Dataset Information

Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues.

Publications

Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues.

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