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.
Highlights
Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent cancers in the oral cavity and has exhibited increased incidence in recent decades [1,2,3]
OTSCC cells compared to normal oralcontrol epithelial control we examined their relative expression in cultured human oral keratinocytes (HOKs) and(HOKs) lines, SCC-25 and transcript expression in cultured human oral keratinocytes and two cell lines, SCC25 and
We found that IL-17F mRNA was expressed at low levels in the most invasive HSC-3 compared with compared with normal
Summary
Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent cancers in the oral cavity and has exhibited increased incidence in recent decades [1,2,3]. Cancers 2019, 11, 650 and tumor recurrence remain the key challenges in the current management of OTSCC patients, and uncovering. Migration, the intravasation of these cells into the vascular system, extravasation into distant tissues, The ability of cancer cells to migrate and invade host tissue is a major requisite for metastasis and metastatic malignant colony formation [8,9]. The subsequent events of the metastatic process are complex and include, in addition to cancer the clinical setting, significant research has been devoted to the potential mediators in the tumor cell migration, the intravasation of these cells into the vascular system, extravasation into distant microenvironment (TME) via whichcolony cancerformation cells proliferate, migrate, and invadeand tissues [10]. To understand halt metastasis cytokine-based immunotherapy has emerged as a novel and attractive therapeutic approach in the clinical setting, significant research has been devoted to the potential mediators in the tumor that targets tumorigenic activity in skin cancers (suchcells as melanoma)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
