POSSIBLE CONTRIBUTION OF ACTIVE MMP2 TO LYMPH-NODE METASTASIS AND SECRETED CATHEPSIN-L TO BONE INVASION OF NEWLY ESTABLISHED HUMAN ORAL-SQUAMOUS-CANCER CELL-LINES

We have established human oral-squamous-cancer cell lines, BHY and HN, derived from non-metastatic cancer and metastatic cancer respectively . We examined the expression of matrix-degrading enzymes and their inh ibitors in these cell lines. Both cell lines expressed pro-matrix meta lloproteinase (MMP)1, proMMP2, proMMP9, membrane-type MMP and urokinas e-type plasminogen activator. In addition to these enzymes, BHY cells secreted proMMP7 and procathepsin L, while HN cells secreted a large a mount of active MMP2. BHY cells secreted a tissue inhibitor of matrix metalloproteinase, TIMP2, but only a trace level of TIMP1. Contrary to BHY cells, HN cells secreted TIMP1, but only a trace level of TIMP2. When we inoculated these cells into the masseter muscle of nude mice, both types of cell formed solid tumors, whose microscopic appearance w as identical to that of the original tumors. BHY tumors were highly di fferentiated squamous-cell carcinomas, and invasive to the masseter mu scle and the mandibular bone. Despite their local aggressiveness, BHY tumors did not metastasize to any distant organs. HN tumors were poorl y differentiated squamous-cell carcinomas, weakly invasive to the musc le, but not to the mandibular bone. However, HN tumors frequently meta stasized to cervical lymph nodes, These results suggest that the net a ctivity of MMP2. (active MMP2/TIMP2) and cathepsin L secreted from can cer cells may contribute respectively to lymph-node metastasis and to bone invasion by oral cancer cells. (C) 1997 Wiley-Liss, Inc.