University of Oulu

Otto Väyrynen, Markku Piippo, Hannaleena Jämsä, Tuomas Väisänen, Carlos E.B. de Almeida, Tuula Salo, Sotiris Missailidis, Maija Risteli, Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro, Experimental Cell Research, Volume 371, Issue 1, 2018, Pages 151-161, ISSN 0014-4827,

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro

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Author: Väyrynen, Otto1,2; Piippo, Markku1,2; Jämsä, Hannaleena1,2;
Organizations: 1Cancer Research and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
3Laboratório de Radiobiologia, Instituto de Radioproteção e Dosimetria, Comissão Nacional de Energia Nuclear, Rio de Janeiro, Brazil
4Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
5HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
6Bio-Manguinhos Institute of Technology in Immunobiologics, FIOCRUZ, Rio de Janeiro, Brazil
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Elsevier, 2018
Publish Date: 2019-08-05


Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and − 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and − 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR.

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Series: Experimental cell research
ISSN: 0014-4827
ISSN-E: 1090-2422
ISSN-L: 0014-4827
Volume: 371
Issue: 1
Pages: 151 - 161
DOI: 10.1016/j.yexcr.2018.08.005
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The work was supported by research grants from Sigrid Juselius Foundation, Cancer Foundation of Finland, Medical Research Center Oulu, Finnish Dental Society Apollonia, Orion Research Foundation, Ida Montin Foundation and research funds from the Medical Faculty of the University of Oulu and Oulu University Hospital special state support for research.
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license