Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform
Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-07-01
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| Series: | Gels |
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| Online Access: | https://www.mdpi.com/2310-2861/3/3/28 |
| _version_ | 1819034196759281664 |
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| author | Hemamylammal Sivakumar Roy Strowd Aleksander Skardal |
| author_facet | Hemamylammal Sivakumar Roy Strowd Aleksander Skardal |
| author_sort | Hemamylammal Sivakumar |
| collection | DOAJ |
| description | Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters on the tumor, and its potential use as a biomarker using a hyaluronic acid hydrogel system capable of elastic modulus tuning and dynamic elastic moduli changes. Experiments were conducted to assess the sensitivity of glioblastoma cell populations with different mutations to varying elastic moduli. Cells with aberrant epithelial growth factor receptor (EGFR) expression have a predilection for a stiffer environment, sensing these parameters through focal adhesion kinase (FAK). Importantly, the inhibition of FAK or EGFR generally resulted in reversed elastic modulus preference. Lastly, we explore the concept of therapeutically targeting the elastic modulus and dynamically reducing it via chemical or enzymatic degradation, both showing the capability to reduce or stunt proliferation rates of these GBM populations. |
| first_indexed | 2024-12-21T07:29:54Z |
| format | Article |
| id | doaj.art-d9a820672d314c07af67ef5c0455fbc5 |
| institution | Directory Open Access Journal |
| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-12-21T07:29:54Z |
| publishDate | 2017-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj.art-d9a820672d314c07af67ef5c0455fbc52022-12-21T19:11:35ZengMDPI AGGels2310-28612017-07-01332810.3390/gels3030028gels3030028Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel PlatformHemamylammal Sivakumar0Roy Strowd1Aleksander Skardal2Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USADepartment of Neurology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USAWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USAGlioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters on the tumor, and its potential use as a biomarker using a hyaluronic acid hydrogel system capable of elastic modulus tuning and dynamic elastic moduli changes. Experiments were conducted to assess the sensitivity of glioblastoma cell populations with different mutations to varying elastic moduli. Cells with aberrant epithelial growth factor receptor (EGFR) expression have a predilection for a stiffer environment, sensing these parameters through focal adhesion kinase (FAK). Importantly, the inhibition of FAK or EGFR generally resulted in reversed elastic modulus preference. Lastly, we explore the concept of therapeutically targeting the elastic modulus and dynamically reducing it via chemical or enzymatic degradation, both showing the capability to reduce or stunt proliferation rates of these GBM populations.https://www.mdpi.com/2310-2861/3/3/28glioblastomaelastic modulustumor growthepidermal growth factor receptorhydrogel |
| spellingShingle | Hemamylammal Sivakumar Roy Strowd Aleksander Skardal Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform Gels glioblastoma elastic modulus tumor growth epidermal growth factor receptor hydrogel |
| title | Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform |
| title_full | Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform |
| title_fullStr | Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform |
| title_full_unstemmed | Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform |
| title_short | Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform |
| title_sort | exploration of dynamic elastic modulus changes on glioblastoma cell populations with aberrant egfr expression as a potential therapeutic intervention using a tunable hyaluronic acid hydrogel platform |
| topic | glioblastoma elastic modulus tumor growth epidermal growth factor receptor hydrogel |
| url | https://www.mdpi.com/2310-2861/3/3/28 |
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