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Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer

By J T Korpi, V Kervinen, H Mäklin, A Väänänen, M Lahtinen, E Läärä, A Ristimäki, G Thomas, M Ylipalosaari, P Åström, C Lopez-Otin, T Sorsa, S Kantola, E Pirilä and T Salo


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, αvβ6 integrin, the laminin-5 γ2-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) α and β. 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

Topics: Translational Therapeutics
Publisher: Nature Publishing Group
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Provided by: PubMed Central
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    1. (2003). Expression of matrix metalloproteinase 8 (MMP-8) and tyrosinase-related protein-1 (TYRP-1) correlates with the absence of metastasis in an isogenic human breast cancer model. Differentiation 71: 114–125 Alho

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