Effects of Vitamin D on tumor cell proliferation and migration, tumor initiation and anti-tumor immune response in head and neck squamous cell carcinomas.

Autor: Brust LA; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Linxweiler M; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Schnatmann J; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Kühn JP; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Knebel M; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Braun FL; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Wemmert S; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Menger MD; Institute of Clinical and Experimental Surgery; Saarland University, Homburg, Germany., Schick B; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany., Holick MF; Department of Physiology and Biophysics; Boston University School of Medicine, Boston, MA, USA., Kuo F; Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Head and Neck Service, Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Morris LGT; Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Head and Neck Service, Immunogenomic Oncology Platform, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Körner S; Department of Otorhinolaryngology, Head and Neck Surgery; Saarland University Medical Center, Homburg, Germany; Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: Sandrina.Koerner@uks.eu.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Nov; Vol. 180, pp. 117497. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1016/j.biopha.2024.117497
Abstrakt: Background: Head and neck squamous cell carcinomas (HNSCCs) are among the six most common cancers, with a constantly poor prognosis. Vitamin D has been found to have antineoplastic and immunomodulatory properties in various cancers. This study investigated the impact of Vitamin D on the initiation and progression as well as antitumor immune response in HNSCCs, both in vitro and in vivo.
Methods: An immunocompetent, orthotopic oral carcinogenesis mouse model was used to examine the influence of Vitamin D 3 substitution on HNSCC initiation and progression in vivo. Tumor immune infiltration was analyzed by immunohistochemistry targeting CD3, CD8, NKR-P1C, FOXP3, and CD163. Two HPV- and two HPV+ HNSCC cell lines were treated with 1,25-dihydroxyvitamin D 3 to analyze effects on tumor cell proliferation, migration and transcriptomic changes using RNA-sequencing, differential gene expression and gene set enrichment analysis.
Results: Vitamin D 3 treatment led to a significant suppression of HNSCC initiation and progression, while also stimulating tumor immune infiltration with CD3+, CD8+ and NKR-P1C+ cells and lowering levels of M2 macrophages and T reg cells in vivo. In vitro experiments showed an inhibition of HNSCC cell proliferation and migration in HPV+ and HPV- cell lines. RNA-sequencing showed significant regulations in IL6 JAK STAT3, hypoxia signaling and immunomodulatory pathways upon Vitamin D 3 treatment.
Conclusion: The findings of our study highlight the promising potential of Vitamin D in the therapeutic repertoire for HNSCC patients given its immune modulating, anti-proliferative and anti-migratory properties. Clinical transferability of those in vitro and in vivo effects should be further validated in clinical trials.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maximilian Linxweiler reports financial support was provided by Else Kroner-Fresenius Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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