University of Oulu

Almahmoudi, R, Salem, A, Hadler-Olsen, E, Svineng, G, Salo, T, Al-Samadi, A. The effect of interleukin-17F on vasculogenic mimicry in oral tongue squamous cell carcinoma. Cancer Sci. 2021; 112: 2223– 2232.

The effect of interleukin-17F on vasculogenic mimicry in oral tongue squamous cell carcinoma

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Author: Almahmoudi, Rabeia1,2; Salem, Abdelhakim1,2; Hadler-Olsen, Elin3,4;
Organizations: 1Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
2Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland
3Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
4The Public Dental Health Service Competence Center of Northern Norway, Tromsø, Norway
5Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
6Medical Research Centre, Oulu University Hospital, Oulu, Finland
7Helsinki University Hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
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Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-06-24


Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL-17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC-3 and SAS) form tube-like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC-25) did not form any VM structures. Droplet-digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC-3 cells expressed VE-cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL-17F inhibited the formation of VM structures in vitro by HSC-3 and reduced almost all VM-related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL-17F through its effect on the VM. Therefore, targeting IL-17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.

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Series: Cancer science
ISSN: 1347-9032
ISSN-E: 1349-7006
ISSN-L: 1347-9032
Volume: 112
Issue: 6
Pages: 2223 - 2232
DOI: 10.1111/cas.14894
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The authors acknowledge the funders of this study: the Doctoral Program in Clinical Research (KLTO), Faculty of Medicine, University of Helsinki; the Emil Aaltonen Foundation; the Minerva Foundation of Medical Research; the Cancer Society of Finland; the Sigrid Jusélius Foundation, and the Jane and Aatos Erkko Foundation.
Copyright information: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.