Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model
Abstract The estrogen receptor (ER) regulates the survival and growth of breast cancer cells, but it is less clear how components of the tissue microenvironment affect ER-mediated responses. We set out to test how human mammary fibroblasts (HMFs) modulate ER signaling and downstream cellular respons...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25461-1 |
| _version_ | 1818681423528198144 |
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| author | Molly M. Morgan Megan K. Livingston Jay W. Warrick Eli M. Stanek Elaine T. Alarid David J. Beebe Brian P. Johnson |
| author_facet | Molly M. Morgan Megan K. Livingston Jay W. Warrick Eli M. Stanek Elaine T. Alarid David J. Beebe Brian P. Johnson |
| author_sort | Molly M. Morgan |
| collection | DOAJ |
| description | Abstract The estrogen receptor (ER) regulates the survival and growth of breast cancer cells, but it is less clear how components of the tissue microenvironment affect ER-mediated responses. We set out to test how human mammary fibroblasts (HMFs) modulate ER signaling and downstream cellular responses. We exposed an organotypic mammary model consisting of a collagen-embedded duct structure lined with MCF7 cells to 17-β estradiol (E2), with and without HMFs in the surrounding matrix. MCF7 cells grown as ductal structures were polarized and proliferated at rates comparable to in vivo breast tissue. In both culture platforms, exposure to E2 increased ER transactivation, increased proliferation, and induced ductal hyperplasia. When the surrounding matrix contained HMFs, the onset and severity of E2-induced ductal hyperplasia was increased due to decreased apoptosis. The reduced apoptosis may be due to fibroblasts modulating ER signaling in MCF7 cells, as suggested by the increased ER transactivation and reduced ER protein in MCF7 cells grown in co-culture. These findings demonstrate the utility of organotypic platforms when studying stromal:epithelial interactions, and add to existing literature that implicate the mammary microenvironment in ER + breast cancer progression. |
| first_indexed | 2024-12-17T10:02:43Z |
| format | Article |
| id | doaj.art-93d31729cd3141899c8dc7350744dfce |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:02:43Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-93d31729cd3141899c8dc7350744dfce2022-12-21T21:53:15ZengNature PortfolioScientific Reports2045-23222018-05-018111310.1038/s41598-018-25461-1Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct modelMolly M. Morgan0Megan K. Livingston1Jay W. Warrick2Eli M. Stanek3Elaine T. Alarid4David J. Beebe5Brian P. Johnson6Department of Biomedical Engineering, University of Wisconsin MadisonDepartment of Biomedical Engineering, University of Wisconsin MadisonDepartment of Biomedical Engineering, University of Wisconsin MadisonDepartment of Biomedical Engineering, University of Wisconsin MadisonDepartment of Oncology, University of Wisconsin MadisonDepartment of Biomedical Engineering, University of Wisconsin MadisonDepartment of Biomedical Engineering, University of Wisconsin MadisonAbstract The estrogen receptor (ER) regulates the survival and growth of breast cancer cells, but it is less clear how components of the tissue microenvironment affect ER-mediated responses. We set out to test how human mammary fibroblasts (HMFs) modulate ER signaling and downstream cellular responses. We exposed an organotypic mammary model consisting of a collagen-embedded duct structure lined with MCF7 cells to 17-β estradiol (E2), with and without HMFs in the surrounding matrix. MCF7 cells grown as ductal structures were polarized and proliferated at rates comparable to in vivo breast tissue. In both culture platforms, exposure to E2 increased ER transactivation, increased proliferation, and induced ductal hyperplasia. When the surrounding matrix contained HMFs, the onset and severity of E2-induced ductal hyperplasia was increased due to decreased apoptosis. The reduced apoptosis may be due to fibroblasts modulating ER signaling in MCF7 cells, as suggested by the increased ER transactivation and reduced ER protein in MCF7 cells grown in co-culture. These findings demonstrate the utility of organotypic platforms when studying stromal:epithelial interactions, and add to existing literature that implicate the mammary microenvironment in ER + breast cancer progression.https://doi.org/10.1038/s41598-018-25461-1 |
| spellingShingle | Molly M. Morgan Megan K. Livingston Jay W. Warrick Eli M. Stanek Elaine T. Alarid David J. Beebe Brian P. Johnson Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model Scientific Reports |
| title | Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model |
| title_full | Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model |
| title_fullStr | Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model |
| title_full_unstemmed | Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model |
| title_short | Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model |
| title_sort | mammary fibroblasts reduce apoptosis and speed estrogen induced hyperplasia in an organotypic mcf7 derived duct model |
| url | https://doi.org/10.1038/s41598-018-25461-1 |
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