University of Oulu

Åström, P., Juurikka, K., Hadler-Olsen, E., Svineng, G., Cervigne, N., Coletta, R., Risteli, J., Kauppila, J., Skarp, S., Kuttner, S., Oteiza, A., Sutinen, M., Salo, T. (2017) The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma. British Journal of Cancer, 117 (7), 1007-1016. doi:10.1038/bjc.2017.249

The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

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Author: Åström, Pirjo1,2,3; Juurikka, Krista1,2; Hadler-Olsen, Elin S4;
Organizations: 1Cancer and Translational Medicine Research Unit, University of Oulu
2Medical Research Center Oulu
3Oulu University Hospital
4Department of Medical Biology, Faculty of Health Sciences, UiT – The Arctic University of Norway
5Department of Morphology and Basic Pathology, Faculty of Medicine of Jundiai (FMJ)
6Department of Oral Diagnosis, School of Dentistry, State University of Campinas
7Department of Clinical Chemistry, University of Oulu
8Northern Finland Laboratory Centre NordLab, Oulu University Hospital
9Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital
10Faculty of Biochemistry and Molecular Medicine, University of Oulu
11Biocenter Oulu
12Center for Life Course Health Research, Faculty of Medicine, University of Oulu
13Medical Imaging Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø – the Arctic University of Norway
14Department of Radiology and Nuclear Medicine, University Hospital of North Norway
15Helsinki University Central Hospital
16Department of Oral Pathology, Institute of Dentistry, Biomedicum, University of Helsinki
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2018-08-03


Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC).

Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples.

Results: MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-β1 (TGF-β1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-β1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells.

Conclusions: The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-β1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.

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Series: British journal of cancer
ISSN: 0007-0920
ISSN-E: 1532-1827
ISSN-L: 0007-0920
Volume: 117
Issue: 7
Pages: 1007 - 1016
DOI: 10.1038/bjc.2017.249
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This research was funded by grants from the Academy of Finland #135573, Sigrid Juselius Foundation, Finnish Cancer Foundation, research funds from the Medical Faculty of the University of Oulu and Oulu University Hospital special state support for research and Medical Research Center Oulu (TS), Finnish Doctoral Program in Oral Sciences, FINDOS, Ida Montin Foundation, Tyyni Tani Foundation (PÅ), Finnish Dental Society Apollonia (MS), Cancer Foundation of Northern Ostrobothnia (PÅ, MS, JHK), Oulu University Research Foundation, Emil Aaltonen Foundation, Mary and Georg C. Ehrnroot Foundation and Finnish Medical Foundation (JHK).
Academy of Finland Grant Number: 135573
Detailed Information: 135573 (Academy of Finland Funding decision)
Dataset Reference: Supplementary information:
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