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Interleukin-17F Has Anti-Tumor Effects in Oral Tongue Cancer

1
Department of Oral and Maxillofacial Diseases, University of Helsinki, Biomedicum Helsinki 1, 00014 Helsinki, Finland
2
Translational Immunology Research Program (TRIMM), University of Helsinki, Biomedicum Helsinki 1, 00014 Helsinki, Finland
3
Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Campinas-SP, Piracicaba, São Paulo 13083-970, Brazil
4
Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA
5
Department of Diagnostics and Oral Medicine, Research Group of Cancer Research and Translational Medicine, Medical Faculty, University of Oulu, 90014 Oulu, Finland
6
Medical Research Centre, Oulu University Hospital, 90220 Oulu, Finland
7
Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
*
Author to whom correspondence should be addressed.
These two authors contributed equally to this work.
Cancers 2019, 11(5), 650; https://doi.org/10.3390/cancers11050650
Received: 30 March 2019 / Revised: 30 April 2019 / Accepted: 8 May 2019 / Published: 11 May 2019
(This article belongs to the Special Issue Targeting Solid Tumors)
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Abstract

We recently showed that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in oral tongue squamous cell carcinoma (OTSCC) patients. However, the underlying mechanisms of such effect remain obscure. Here, we used qRT-PCR to assess the expression of IL-17F and its receptors (IL-17RA and IL-17RC) in two OTSCC cell lines (HSC-3 and SCC-25) and in normal human oral keratinocytes (HOKs). IL-17F effects on cancer cell proliferation, migration, and invasion were studied using a live-imaging IncuCyte system, and a Caspase-3/7 reagent was used for testing apoptosis. 3D tumor spheroids were utilized to assess the impact of IL-17F on invasion with or without cancer-associated fibroblasts (CAFs). Tube-formation assays were used to examine the effects of IL-17F on angiogenesis using human umbilical vein endothelial cells (HUVEC). OTSCC cells express low levels of IL-17F, IL-17RA, and IL-17RC mRNA compared with HOKs. IL-17F inhibited cell proliferation and random migration of highly invasive HSC-3 cells. CAFs promoted OTSCC invasion in tumor spheroids, whereas IL-17F eliminated such effect. IL-17F suppressed HUVEC tube formation in a dose-dependent manner. Collectively, we suggest that IL-17F counteracts the pro-tumorigenic activity in OTSCC. Due to its downregulation in tumor cells and inhibitory activity in in vitro cancer models, targeting IL-17F or its regulatory pathways could lead to promising immunotherapeutic strategies against OTSCC. View Full-Text
Keywords: interleukin-17F; cancer immunotherapy; cytokine therapy; tongue cancer; oral squamous cell carcinoma; proliferation; invasion; apoptosis; angiogenesis; HUVEC cells interleukin-17F; cancer immunotherapy; cytokine therapy; tongue cancer; oral squamous cell carcinoma; proliferation; invasion; apoptosis; angiogenesis; HUVEC cells
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Almahmoudi, R.; Salem, A.; Murshid, S.; Dourado, M.R.; Apu, E.H.; Salo, T.; Al-Samadi, A. Interleukin-17F Has Anti-Tumor Effects in Oral Tongue Cancer. Cancers 2019, 11, 650.

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