Expression of type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in newly established human oral malignant tumor lines.

Abstract

We have established 11 human oral tumor lines maintained as in subcutaneous xenografts in BALB/c athymic nude mice, and examined their metastatic and invasive characteristics, and expression of type IV collagen-degrading metalloproteinases and their intrinsic inhibitors (TIMPs). These tumor lines have approximately maintained the histological appearance of the parental tumors. Generally, human tumors maintained subcutaneously in nude mice metastasize only very rarely. However, one mesenchymal tumor line, a malignant melanoma designated MTN, was found to metastasize spontaneously to the lung and a lysate of the MTN cells had a high level of type IV collagenolytic activity. Among epithelial tumor lines, SKH, derived from squamous cell carcinoma, showed high expression of TIMP-1 in Northern blotting and had low type IV collagenolytic activity. SN, derived from squamous cell carcinoma, also showed low type IV collagenolytic activity. These two squamous cell carcinoma lines showed a non-invasive growth pattern when they were implanted orthotopically into the tongues of athymic nude mice. By contrast, tumor lines which showed higher type IV collagenolytic activity had a tendency to grow invasively in mouse tongue. These findings suggest that our 11 newly established tumor lines may provide useful systems for studies of tumor biology and therapy.