Mechanical activation and expression of HSP27 in epithelial ovarian cancer
Abstract Understanding the complex biomechanical tumor microenvironment (TME) is of critical importance in developing the next generation of anti-cancer treatment strategies. This is especially true in epithelial ovarian cancer (EOC), the deadliest of the gynecologic cancers due to recurrent disease...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52992-7 |
| _version_ | 1797274888217559040 |
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| author | Molly Buckley Maranda Kramer Bronte Johnson Gillian Huskin Joel Berry Mary Kathryn Sewell-Loftin |
| author_facet | Molly Buckley Maranda Kramer Bronte Johnson Gillian Huskin Joel Berry Mary Kathryn Sewell-Loftin |
| author_sort | Molly Buckley |
| collection | DOAJ |
| description | Abstract Understanding the complex biomechanical tumor microenvironment (TME) is of critical importance in developing the next generation of anti-cancer treatment strategies. This is especially true in epithelial ovarian cancer (EOC), the deadliest of the gynecologic cancers due to recurrent disease or chemoresistance. However, current models of EOC progression provide little control or ability to monitor how changes in biomechanical parameters alter EOC cell behaviors. In this study, we present a microfluidic device designed to permit biomechanical investigations of the ovarian TME. Using this microtissue system, we describe how biomechanical stimulation in the form of tensile strains upregulate phosphorylation of HSP27, a heat shock protein implicated in ovarian cancer chemoresistance. Furthermore, EOC cells treated with strain demonstrate decreased response to paclitaxel in the in vitro vascularized TME model. The results provide a direct link to biomechanical regulation of HSP27 as a mediator of EOC chemoresistance, possibly explaining the failure of such therapies in some patients. The work presented here lays a foundation to elucidating mechanobiological regulation of EOC progression, including chemoresistance and could provide novel targets for anti-cancer therapeutics. |
| first_indexed | 2024-03-07T15:04:36Z |
| format | Article |
| id | doaj.art-b716d870868346a59ce4a06cd270f492 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:04:36Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b716d870868346a59ce4a06cd270f4922024-03-05T18:58:16ZengNature PortfolioScientific Reports2045-23222024-02-0114111610.1038/s41598-024-52992-7Mechanical activation and expression of HSP27 in epithelial ovarian cancerMolly Buckley0Maranda Kramer1Bronte Johnson2Gillian Huskin3Joel Berry4Mary Kathryn Sewell-Loftin5Department of Biomedical Engineering, University of Alabama at BirminghamDepartment of Biomedical Engineering, University of Alabama at BirminghamDepartment of Biomedical Engineering, University of Alabama at BirminghamDepartment of Biomedical Engineering, University of Alabama at BirminghamDepartment of Biomedical Engineering, University of Alabama at BirminghamDepartment of Biomedical Engineering, University of Alabama at BirminghamAbstract Understanding the complex biomechanical tumor microenvironment (TME) is of critical importance in developing the next generation of anti-cancer treatment strategies. This is especially true in epithelial ovarian cancer (EOC), the deadliest of the gynecologic cancers due to recurrent disease or chemoresistance. However, current models of EOC progression provide little control or ability to monitor how changes in biomechanical parameters alter EOC cell behaviors. In this study, we present a microfluidic device designed to permit biomechanical investigations of the ovarian TME. Using this microtissue system, we describe how biomechanical stimulation in the form of tensile strains upregulate phosphorylation of HSP27, a heat shock protein implicated in ovarian cancer chemoresistance. Furthermore, EOC cells treated with strain demonstrate decreased response to paclitaxel in the in vitro vascularized TME model. The results provide a direct link to biomechanical regulation of HSP27 as a mediator of EOC chemoresistance, possibly explaining the failure of such therapies in some patients. The work presented here lays a foundation to elucidating mechanobiological regulation of EOC progression, including chemoresistance and could provide novel targets for anti-cancer therapeutics.https://doi.org/10.1038/s41598-024-52992-7 |
| spellingShingle | Molly Buckley Maranda Kramer Bronte Johnson Gillian Huskin Joel Berry Mary Kathryn Sewell-Loftin Mechanical activation and expression of HSP27 in epithelial ovarian cancer Scientific Reports |
| title | Mechanical activation and expression of HSP27 in epithelial ovarian cancer |
| title_full | Mechanical activation and expression of HSP27 in epithelial ovarian cancer |
| title_fullStr | Mechanical activation and expression of HSP27 in epithelial ovarian cancer |
| title_full_unstemmed | Mechanical activation and expression of HSP27 in epithelial ovarian cancer |
| title_short | Mechanical activation and expression of HSP27 in epithelial ovarian cancer |
| title_sort | mechanical activation and expression of hsp27 in epithelial ovarian cancer |
| url | https://doi.org/10.1038/s41598-024-52992-7 |
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