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, avb6 integrin, the laminin-5 g2-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 wildtype 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) a and b. 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.

Ten healthy male volunteers were exposed to the dry heat of a Finnish sauna (+80 degrees C) for 1 h twice a day for a period of 7 days. After each exposure rectal temperature rose by 0.8-1.1 degrees C and body weight dropped by 0.7-0.9 kg. The systolic blood pressure recorded 3-5 min after the sauna did not change during the experiments but the diastolic blood pressure decreased by 7-37 mmHg (P less than 0.05). The pulse rate rose from 75-80 to 106-116 beats min-1 (P less than 0.05) after the sauna. The increased responses of pulse and temperature adapted to heat exposures so that they were significantly lower after the 3rd day (rectal temperature) or after 6th day (pulse). Metabolic rate increased by 25-33% (P less than 0.01) after the first day. Serum total proteins, Hb and Htc were significantly increased on the 1st and 3rd days but not later, although the dehydration in response to sauna was unchanged as judged from the weight losses. Serum K, Na and Fe were significantly decreased on the 3rd and 7th day indicating that special attention should be given to the electrolyte balance in long-lasting intense heat exposure. No ECG changes were found in recordings taken on the 7th day.

(LB-T)S U M M A R Y Collagen XVII (BP180) is a hemidesmosomal transmembrane component that has been hypothesized to participate in keratinocyte adhesion and motility. Using immunohistochemical (IHC) and in situ hybridization (ISH) methods, we showed downregulation of collagen XVII in basal cells in mild dysplasias and upregulation in suprabasal keratinocytes in moderate and severe dysplasias as well as in the central cells of grade II and III squamous cell carcinomas (SCCs). Overexpression of collagen XVII was found at the invasive front of the tumors. Collagen XVII and its cleaved ectodomain were characterized from culture extracts and precipitates of oral keratinocytes, tongue carcinoma cells, and tumor tissue extract. Malignant cell lines exhibited increased collagen XVII expression in immunoblotting analysis. In oral keratinocytes, collagen XVII gene expression was significantly induced by PMA but not by the inflammatory cytokines TGF-␤ 1, TNF-␣ , EGF, IL-1 ␤ , and IL-6. These results indicate altered expression of collagen XVII at different stages of carcinogenesis and suggest a correlation between overexpression of collagen XVII and tumor progression. The reduced collagen XVII expression at the early step of carcinogenesis may reflect disturbed keratinocyte adhesion to the basement membrane.