We recently showed that IL-17F expression correlates with better overall survival in oral tongue cancer (OTSCC) patients. Moreover, IL-17F inhibited OTSCC cell proliferation and migration. However, anti-angiogenic drugs showed limited effects in cancer treatment, where cancer cells use “de novo” vessel-like channels called vasculogenic mimicry (VM) to enhance nutrient supplies. Therefore, we aimed to investigate the vasculogenic mimicry in OTSCC and the potential effect of IL-17F on such phenomenon.
we used qRT-PCR immunostaining, and Western blotting methods to investigate the expression of VM-related markers (such as CD31, CD34 and VEGFA) at both gene and protein level, respectively. The capacity to create tube-like (channel-like) structures in 3D matrices were assessed in two different OTSCC-derived cell lines (the highly-aggressive HSC-3; and the less-invasive SCC-25). Tube-formation assays were used to examine the effects of IL-17F on angiogenesis using cancer cell lines and human umbilical vein endothelial cells (HUVEC), with or without antiangiogenic agents.
OTSCC cell lines showed differential expression of CD31, CD34 and VEGFA genes. The level of such markers was dependent on the 3D matrix (Matrigel). OTSCC cells expressed abundant CD31 and CD34 receptors. In addition, we confirmed the presence of VM in more advanced-stages of OTSCC patients. Importantly, both HSC-3 and SCC-25 created channel-like structures when cultured on Matrigel matrix. Interestingly, IL-17F inhibited the tube-formation in HUVEC cells, and showed promising anti-angiogenic effects in vitro.
Our findings confirm the role of VM in OTSCC carcinogenesis. Here, we suggest that IL-17F counteracts the tumorigenic activity in OTSCC, in part, through the antiangiogenic effect in the tumour microenvironment, and hence further studies are warranted. Harnessing IL-17F in the current management approaches in advanced OTSCC patients may lead to promising immunotherapeutic strategies against OTSCC.
University of Helsinki.
University of Helsinki, Doctoral program in clinical research (KLTO).
The author has declared no conflicts of interest.