1. ¹Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Oulu and Oulu University Hospital, Oulu, Finland
2. ²Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, Oulu, Finland
3. ³Division of Statistics, Department of Mathematical Sciences, University of Oulu, Oulu, Finland
4. ⁴Department of Pathology, University of Helsinki, Helsinki, Finland
5. ⁵Tumor Biology Laboratory, Cancer Research UK Clinical Centre, Barts and the London School of Medicine and Dentistry, London, UK
6. ⁶Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
7. ⁷Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Dr T Salo, Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, PO Box 5281, Oulu 90014, Finland. E-mail: tuula.salo@oulu.fi

⁸Equal supervisors.

Revised 21 December 2007; Accepted 9 January 2008; Published online 5 February 2008.

Abstract

Squamous cell carcinoma (SCC) of the tongue is the most common cancer in the oral cavity and has a high mortality rate. A total of 90 mobile tongue SCC samples were analysed for Bryne's malignancy scores, microvascular density, and thickness of the SCC sections. In addition, the staining pattern of cyclooxygenase-2, v6 integrin, the laminin-5 2-chain, and matrix metalloproteinases (MMPs) -2, -7, -8, -9, -20, and -28 were analysed. The expression of MMP-8 (collagenase-2) was positively associated with improved survival of the patients and the tendency was particularly prominent in females. No sufficient evidence for a correlation with the clinical outcome was found for any other immunohistological marker. To test the protective role of MMP-8 in tongue carcinogenesis, MMP-8 knockout mice were used. MMP-8 deficient female mice developed tongue SCCs at a significantly higher incidence than wild-type mice exposed to carcinogen 4-Nitroquinoline-N-oxide. Consistently, oestrogen-induced MMP-8 expression in cultured HSC-3 tongue carcinoma cells, and MMP-8 cleaved oestrogen receptor (ER) and . According to these data, we propose that, contrary to the role of most proteases produced by human carcinomas, MMP-8 has a protective, probably oestrogen-related role in the growth of mobile tongue SCCs.