Abstract
Purpose
The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist.
Methods
A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed.
Results
The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis.
Conclusions
The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.
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Data availability
All analyzed and raw derivative data are available on request.
Change history
16 March 2024
The original version of the article was revised to correct the error in the article title.
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Funding
This work was supported by grants from Agencia Nacional de Investigación y Desarrollo (ANID) de Chile: Fondecyt Regular 1190775 to WAGA, Fondecyt Regular 1230875 to FAM, Fondecyt de Iniciación 11180531 to IEG, and ANID-Basal funding for Scientific and Technological Center of Excellence, IMPACT, #FB210024 to FAM & WAGA.
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WAGA, RDC, IEG: Study concept and design. WAGA, JM, CG, BGP, RMF, SOP, IEG: Performed research and analyzed data. WAGA, CLB, FAM, IEG: Resource provision. WGA, RDC, IEG: Writing-original draft. All authors: Writing-review and editing.
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For research using human specimens, the study was approved by Research Ethics Committee of the Universidad de los Andes (CEC2022020) and the Research Ethics Committee of the Universidad de Valparaíso (CEC195-19), following the Helsinki Declaration and its later amendments. Approval for the animal experiments was granted by the Bioethics Committee for Animal Studies of Universidad de Valparaíso (BEA135-19) and Universidad de los Andes (CEC2022020). The study was also approved by the Universidad de Valparaíso Biosecurity Committee (BS0001-19).
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González-Arriagada, W.A., Coletta, R.D., Lozano-Burgos, C. et al. CCR5/CCL5 axis is linked to a poor outcome, and inhibition reduces metastasis in oral squamous cell carcinoma. J Cancer Res Clin Oncol 149, 17335–17346 (2023). https://doi.org/10.1007/s00432-023-05443-1
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DOI: https://doi.org/10.1007/s00432-023-05443-1