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

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, alphavbeta6 integrin, the laminin-5 gamma2-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) alpha and beta. 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.

• Authors: J T Korpi, V Kervinen, H Mäklin, A Väänänen, M Lahtinen, E Läärä, A Ristimäki, G Thomas, M Ylipalosaari, P Aström, C Lopez-Otin, T Sorsa, S Kantola, E Pirilä, T Salo
• Journal: British journal of cancer (Br J Cancer) Vol. 98 Issue 4 Pg. 766-75 (Feb 26 2008) ISSN: 0007-0920 [Print] England
• PMID: 18253113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Carcinogens
• Estrogen Receptor alpha
• Estrogen Receptor beta
• RNA, Messenger
• 4-Nitroquinoline-1-oxide
• Matrix Metalloproteinase 8

Topics

• 4-Nitroquinoline-1-oxide (toxicity)
• Adult
• Aged
• Aged, 80 and over
• Animals
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Carcinogens (toxicity)
• Carcinoma, Squamous Cell (chemically induced, enzymology, prevention & control)
• Estrogen Receptor alpha (metabolism)
• Estrogen Receptor beta (metabolism)
• Female
• Humans
• Immunoenzyme Techniques
• Male
• Matrix Metalloproteinase 8 (physiology)
• Mice
• Mice, Knockout
• Middle Aged
• Mouth Neoplasms (enzymology, pathology)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tongue Neoplasms (enzymology, pathology, prevention & control)
• Tumor Cells, Cultured