Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck
Abundance and signaling of the epidermal growth factor receptor (EGFR) and programmed cell death protein ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC) are not only genetically determined but are also subject to the traits of the tumor microenvironment, which has hitherto not been...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.623964/full |
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| author | Sebastian Zahnreich Senayit Gebrekidan Gabriele Multhoff Gabriele Multhoff Peter Vaupel Heinz Schmidberger Arnulf Mayer |
| author_facet | Sebastian Zahnreich Senayit Gebrekidan Gabriele Multhoff Gabriele Multhoff Peter Vaupel Heinz Schmidberger Arnulf Mayer |
| author_sort | Sebastian Zahnreich |
| collection | DOAJ |
| description | Abundance and signaling of the epidermal growth factor receptor (EGFR) and programmed cell death protein ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC) are not only genetically determined but are also subject to the traits of the tumor microenvironment, which has hitherto not been clarified completely. We investigated the impact of hypoxia on the EGFR system and on PD-L1 in six HPV negative HNSCC cell lines in vitro and in FaDu xenografts in vivo. Protein levels of EGFR, AKT, pAKT, ERK1/2, pERK1/2, CA IX, cleaved PARP (apoptosis), LC3B (autophagy), and PD-L1 were quantified by western blot after oxygen deprivation or CoCl2, staurosporine, and erlotinib treatment. In FaDu xenograft tumors the expression of EGFR, CA IX andCD34 staining were analyzed. Reduced oxygen supply strongly downregulated EGFR protein levels and signaling in FaDu cells in vitro and in vivo, and a transient downregulation of EGFR signaling was found in three other HNSCC cell lines. PD-L1 was affected by oxygen deprivation in only one HNSCC cell line showing increased protein amounts. The results of this study indicate a significant impact of the traits of the tumor microenvironment on crucial molecular targets of cancer therapies with high clinical relevance for therapy resistance and response in HNSCC. |
| first_indexed | 2024-12-23T23:29:09Z |
| format | Article |
| id | doaj.art-321e7d79611349e891c08c8ee297b7de |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-23T23:29:09Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-321e7d79611349e891c08c8ee297b7de2022-12-21T17:26:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011110.3389/fonc.2021.623964623964Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and NeckSebastian Zahnreich0Senayit Gebrekidan1Gabriele Multhoff2Gabriele Multhoff3Peter Vaupel4Heinz Schmidberger5Arnulf Mayer6Department of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, Mainz, GermanyDepartment of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, Mainz, GermanyRadiation Immuno-Oncology Project Group, Central Institute for Translational Cancer Research, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyDepartment of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyDepartment of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, Mainz, GermanyDepartment of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, Mainz, GermanyDepartment of Radiation Oncology and Radiation Therapy, University Medical Center Mainz, Mainz, GermanyAbundance and signaling of the epidermal growth factor receptor (EGFR) and programmed cell death protein ligand 1 (PD-L1) in head and neck squamous cell carcinoma (HNSCC) are not only genetically determined but are also subject to the traits of the tumor microenvironment, which has hitherto not been clarified completely. We investigated the impact of hypoxia on the EGFR system and on PD-L1 in six HPV negative HNSCC cell lines in vitro and in FaDu xenografts in vivo. Protein levels of EGFR, AKT, pAKT, ERK1/2, pERK1/2, CA IX, cleaved PARP (apoptosis), LC3B (autophagy), and PD-L1 were quantified by western blot after oxygen deprivation or CoCl2, staurosporine, and erlotinib treatment. In FaDu xenograft tumors the expression of EGFR, CA IX andCD34 staining were analyzed. Reduced oxygen supply strongly downregulated EGFR protein levels and signaling in FaDu cells in vitro and in vivo, and a transient downregulation of EGFR signaling was found in three other HNSCC cell lines. PD-L1 was affected by oxygen deprivation in only one HNSCC cell line showing increased protein amounts. The results of this study indicate a significant impact of the traits of the tumor microenvironment on crucial molecular targets of cancer therapies with high clinical relevance for therapy resistance and response in HNSCC.https://www.frontiersin.org/articles/10.3389/fonc.2021.623964/fullhead and neck cancerepidermal growth factor receptorRas-MAPK pathwayPI3K/AKTPD-L1hypoxia |
| spellingShingle | Sebastian Zahnreich Senayit Gebrekidan Gabriele Multhoff Gabriele Multhoff Peter Vaupel Heinz Schmidberger Arnulf Mayer Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck Frontiers in Oncology head and neck cancer epidermal growth factor receptor Ras-MAPK pathway PI3K/AKT PD-L1 hypoxia |
| title | Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck |
| title_full | Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck |
| title_fullStr | Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck |
| title_full_unstemmed | Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck |
| title_short | Oxygen Deprivation Modulates EGFR and PD-L1 in Squamous Cell Carcinomas of the Head and Neck |
| title_sort | oxygen deprivation modulates egfr and pd l1 in squamous cell carcinomas of the head and neck |
| topic | head and neck cancer epidermal growth factor receptor Ras-MAPK pathway PI3K/AKT PD-L1 hypoxia |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.623964/full |
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