Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform
Abstract Tumor resistance to chemotherapy is a common cause of cancer recurrence in patients with head and neck squamous cell carcinoma. The goal of this study is to establish and characterize a chemoresistant laryngeal cancer cell model and test its potential utility for chemosensitizing therapy. A...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10741 |
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| author | Christian R. Moya‐Garcia Meghana Munipalle Alain Pacis Nader Sadeghi Maryam Tabrizian Nicole Y. K. Li‐Jessen |
| author_facet | Christian R. Moya‐Garcia Meghana Munipalle Alain Pacis Nader Sadeghi Maryam Tabrizian Nicole Y. K. Li‐Jessen |
| author_sort | Christian R. Moya‐Garcia |
| collection | DOAJ |
| description | Abstract Tumor resistance to chemotherapy is a common cause of cancer recurrence in patients with head and neck squamous cell carcinoma. The goal of this study is to establish and characterize a chemoresistant laryngeal cancer cell model and test its potential utility for chemosensitizing therapy. At the genotypic level, RNA sequencing confirmed that the cells acquired putative resistance with upregulated docetaxel‐resistant (DR) genes (e.g., TUBB3, CYP24A1) and signaling pathways (e.g., PI3K/mTOR, autophagy). For phenotypic analysis, DR cells were co‐cultured with laryngeal fibroblasts in a 2‐channel microfluidic chip that mimics a hypoxic tumor core in vivo. A drug sensitivity test with a chemosensitizer, metformin (MTF), was performed on the laryngeal tumor‐on‐a‐chip. Compared to non‐treated controls, MTF‐primed cancer cells exhibit higher sensitivity to docetaxel (DTX), that is, cell death. Collectively, this resistance‐acquired cell model displayed presumed genotypic and phenotypic profiles of chemoresistance providing a viable option for testing new therapeutic strategies for restoring tumor sensitivity to DTX. |
| format | Article |
| id | doaj-art-182f3ef354dd447a9d6fecdaaa3ee808 |
| institution | OA Journals |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-182f3ef354dd447a9d6fecdaaa3ee8082025-08-20T02:31:30ZengWileyBioengineering & Translational Medicine2380-67612025-05-01103n/an/a10.1002/btm2.10741Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platformChristian R. Moya‐Garcia0Meghana Munipalle1Alain Pacis2Nader Sadeghi3Maryam Tabrizian4Nicole Y. K. Li‐Jessen5Department of Biomedical Engineering, Faculty of Medicine and Health Sciences McGill University Quebec CanadaDepartment of Biomedical Engineering, Faculty of Medicine and Health Sciences McGill University Quebec CanadaCanadian Centre for Computational Genomics (C3G) McGill University Montreal Quebec CanadaDepartment of Otolaryngology – Head and Neck Surgery McGill University, MUHC (Royal Victoria Hospital) Montreal Quebec CanadaDepartment of Biomedical Engineering, Faculty of Medicine and Health Sciences McGill University Quebec CanadaDepartment of Biomedical Engineering, Faculty of Medicine and Health Sciences McGill University Quebec CanadaAbstract Tumor resistance to chemotherapy is a common cause of cancer recurrence in patients with head and neck squamous cell carcinoma. The goal of this study is to establish and characterize a chemoresistant laryngeal cancer cell model and test its potential utility for chemosensitizing therapy. At the genotypic level, RNA sequencing confirmed that the cells acquired putative resistance with upregulated docetaxel‐resistant (DR) genes (e.g., TUBB3, CYP24A1) and signaling pathways (e.g., PI3K/mTOR, autophagy). For phenotypic analysis, DR cells were co‐cultured with laryngeal fibroblasts in a 2‐channel microfluidic chip that mimics a hypoxic tumor core in vivo. A drug sensitivity test with a chemosensitizer, metformin (MTF), was performed on the laryngeal tumor‐on‐a‐chip. Compared to non‐treated controls, MTF‐primed cancer cells exhibit higher sensitivity to docetaxel (DTX), that is, cell death. Collectively, this resistance‐acquired cell model displayed presumed genotypic and phenotypic profiles of chemoresistance providing a viable option for testing new therapeutic strategies for restoring tumor sensitivity to DTX.https://doi.org/10.1002/btm2.10741chemoresistancedocetaxelmetforminlaryngeal cancerhypoxiasenescence |
| spellingShingle | Christian R. Moya‐Garcia Meghana Munipalle Alain Pacis Nader Sadeghi Maryam Tabrizian Nicole Y. K. Li‐Jessen Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform Bioengineering & Translational Medicine chemoresistance docetaxel metformin laryngeal cancer hypoxia senescence |
| title | Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform |
| title_full | Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform |
| title_fullStr | Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform |
| title_full_unstemmed | Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform |
| title_short | Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform |
| title_sort | establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor on a chip platform |
| topic | chemoresistance docetaxel metformin laryngeal cancer hypoxia senescence |
| url | https://doi.org/10.1002/btm2.10741 |
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