ROLE OF THE MATRIX METALLOPROTEINASE AND TISSUE INHIBITORS OF METALLOPROTEINASE FAMILIES IN NONINVASIVE AND INVASIVE TUMORS TRANSPLANTED INMICE WITH SEVERE COMBINED IMMUNODEFICIENCY

Objectives. To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelia l cancers, we studied gene expressions of MMPs, TIMPs, and membrane-ty pe 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tum or lines transplanted in mice with severe combined immunodeficiency (S CID). Methods. The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invad es without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7 , 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by s emiquantitative polymerase chain reaction analysis. Results. Significa ntly higher gene expression of MMP-2 was detected in the invasive UCT- 2 tumor line than in the noninvasive UCT-1 tumor line. Although both t umor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of M T1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor li ne. The other MMPs or TIMPs were not detected in either of the lines. Conclusions. MMP-2 and MT1-MMP may have an important role in the invas ion mechanism of urothelial cancers. (C) 1998, Elsevier Science Inc. A ll rights reserved.