Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer.
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.
Korpi
J T
JT
Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Oulu and Oulu University Hospital, Oulu, Finland.
Kervinen
V
V
Mäklin
H
H
Väänänen
A
A
Lahtinen
M
M
Läärä
E
E
Ristimäki
A
A
Thomas
G
G
Ylipalosaari
M
M
Aström
P
P
Lopez-Otin
C
C
Sorsa
T
T
Kantola
S
S
Pirilä
E
E
Salo
T
T
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002273:Carcinogens; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D015112:4-Nitroquinoline-1-oxide; D020784:Matrix Metalloproteinase 8