EXPRESSION OF TYPE-IV COLLAGEN-DEGRADING METALLOPROTEINASES AND TISSUE INHIBITORS OF METALLOPROTEINASES IN NEWLY ESTABLISHED HUMAN ORAL MALIGNANT-TUMOR LINES

We have established 11 human oral tumor lines maintained as in subcuta neous xenografts in BALB/c athymic nude mice, and examined their metas tatic and invasive characteristics, and expression of Type IV collagen -degrading metalloproteinases and their intrinsic inhibitors (TIMPs). These tumor lines have approximately maintained the histological appea rance of the parental tumors. Generally, human tumors maintained subcu taneously in nude mice metastasize only very rarely. However, one mese nchymal tumor line, a malignant melanoma designated MTN, was found to metastasize spontaneously to the lung and a lysate of the MTN cells ha d a high level of type IV collagenolytic activity. Among epithelial tu mor lines, SKH, derived from squamous cell carcinoma, showed high expr ession of TIMP-1 in Northern blotting and had low type IV collagenolyt ic activity. SN, derived from squamous cell carcinoma, also showed low type IV collagenolytic activity. These two squamous cell carcinoma li nes showed a non-invasive growth pattern when they were implanted orth otopically into the tongues of athymic nude mice. By contrast, tumor l ines which showed higher type IV collagenolytic activity had a tendenc y to grow invasively in mouse tongue. These findings suggest that our 11 newly established tumor lines may provide useful systems for studie s of tumor biology and therapy.