The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082
Glioblastoma Multiforme (GBM) cells interact with a complex, heterogeneous tumor microenvironment (TME). This TME consists of astrocytes, endothelial cells, microglia, and pericytes, which together play a role in GBM progression and resistance. However, there are not enough in vitro three-dimensiona...
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| Format: | Article |
| Language: | English |
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IEEE
2022-01-01
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| Series: | IEEE Access |
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| Online Access: | https://ieeexplore.ieee.org/document/9694593/ |
| _version_ | 1798022453036843008 |
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| author | Sadaf E. Pustchi Charlotte Mae K. Waits Naze Gul Avci Lindsey Mcgill Yasemin M. Akay Metin Akay |
| author_facet | Sadaf E. Pustchi Charlotte Mae K. Waits Naze Gul Avci Lindsey Mcgill Yasemin M. Akay Metin Akay |
| author_sort | Sadaf E. Pustchi |
| collection | DOAJ |
| description | Glioblastoma Multiforme (GBM) cells interact with a complex, heterogeneous tumor microenvironment (TME). This TME consists of astrocytes, endothelial cells, microglia, and pericytes, which together play a role in GBM progression and resistance. However, there are not enough in vitro three-dimensional (3D) models to study the effect of the TME on GBM resistance to chemotherapeutics. In this study, we created a GBM TME by culturing GBM cells with media that had been conditioned by human astrocytes (HA) in 3D microwells. In order to investigate the effect of the TME on GBM resistance to chemotherapeutic agents, cells were treated with Temozolomide (TMZ) in combination with nuclear factor-<inline-formula> <tex-math notation="LaTeX">$\kappa \text{B}$ </tex-math></inline-formula> (NF-<inline-formula> <tex-math notation="LaTeX">$\kappa \text{B}$ </tex-math></inline-formula>) inhibitor “Bay 11-7082”. We examined the influence of HA conditioned media (CM) on the expression of various genes and the response to TMZ and Bay 11–7082 in our 3D cultures. Our data suggested that proteins and metabolic factors produced by HA in CM can significantly alter GBM response to chemotherapeutics. Our results indicated lower levels of apoptosis- and drug resistance-related genes were detected in LN229 and U87 cultures in their respective cell culture media compared to HA CM. Our results confirmed HA affect GBM response to therapy. |
| first_indexed | 2024-04-11T17:30:22Z |
| format | Article |
| id | doaj.art-a664375dc9884d92b0ea36990a6d8786 |
| institution | Directory Open Access Journal |
| issn | 2169-3536 |
| language | English |
| last_indexed | 2024-04-11T17:30:22Z |
| publishDate | 2022-01-01 |
| publisher | IEEE |
| record_format | Article |
| series | IEEE Access |
| spelling | doaj.art-a664375dc9884d92b0ea36990a6d87862022-12-22T04:12:07ZengIEEEIEEE Access2169-35362022-01-0110128821288810.1109/ACCESS.2022.31468879694593The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082Sadaf E. Pustchi0Charlotte Mae K. Waits1https://orcid.org/0000-0002-9150-7530Naze Gul Avci2Lindsey Mcgill3Yasemin M. Akay4Metin Akay5https://orcid.org/0000-0002-2988-4669Department of Biomedical Engineering, University of Houston, Houston, TX, USADepartment of Biomedical Engineering, University of Houston, Houston, TX, USADepartment of Biomedical Engineering, University of Houston, Houston, TX, USADepartment of Biomedical Engineering, University of Houston, Houston, TX, USADepartment of Biomedical Engineering, University of Houston, Houston, TX, USADepartment of Biomedical Engineering, University of Houston, Houston, TX, USAGlioblastoma Multiforme (GBM) cells interact with a complex, heterogeneous tumor microenvironment (TME). This TME consists of astrocytes, endothelial cells, microglia, and pericytes, which together play a role in GBM progression and resistance. However, there are not enough in vitro three-dimensional (3D) models to study the effect of the TME on GBM resistance to chemotherapeutics. In this study, we created a GBM TME by culturing GBM cells with media that had been conditioned by human astrocytes (HA) in 3D microwells. In order to investigate the effect of the TME on GBM resistance to chemotherapeutic agents, cells were treated with Temozolomide (TMZ) in combination with nuclear factor-<inline-formula> <tex-math notation="LaTeX">$\kappa \text{B}$ </tex-math></inline-formula> (NF-<inline-formula> <tex-math notation="LaTeX">$\kappa \text{B}$ </tex-math></inline-formula>) inhibitor “Bay 11-7082”. We examined the influence of HA conditioned media (CM) on the expression of various genes and the response to TMZ and Bay 11–7082 in our 3D cultures. Our data suggested that proteins and metabolic factors produced by HA in CM can significantly alter GBM response to chemotherapeutics. Our results indicated lower levels of apoptosis- and drug resistance-related genes were detected in LN229 and U87 cultures in their respective cell culture media compared to HA CM. Our results confirmed HA affect GBM response to therapy.https://ieeexplore.ieee.org/document/9694593/Glioblastoma3D modelstumor microenvironmentco-culture |
| spellingShingle | Sadaf E. Pustchi Charlotte Mae K. Waits Naze Gul Avci Lindsey Mcgill Yasemin M. Akay Metin Akay The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 IEEE Access Glioblastoma 3D models tumor microenvironment co-culture |
| title | The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 |
| title_full | The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 |
| title_fullStr | The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 |
| title_full_unstemmed | The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 |
| title_short | The Influence of Human Astrocyte-Conditioned Media on Glioblastoma Multiforme Response to Temozolomide and Bay 11-7082 |
| title_sort | influence of human astrocyte conditioned media on glioblastoma multiforme response to temozolomide and bay 11 7082 |
| topic | Glioblastoma 3D models tumor microenvironment co-culture |
| url | https://ieeexplore.ieee.org/document/9694593/ |
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