Role of the matrix metalloproteinase and tissue inhibitors of metalloproteinase families in noninvasive and invasive tumors transplanted in mice with severe combined immunodeficiency.
OBJECTIVE
To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID).


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 invades 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 semiquantitative polymerase chain reaction analysis.


RESULTS
Significantly 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 tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. 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 invasion mechanism of urothelial cancers.
Furukawa
A
A
Department of Urology, School of Medicine, The University of Tokushima, Japan.
Tsuji
M
M
Nishitani
M
M
Kanda
K
K
Inoue
Y
Y
Kanayama
H
H
Kagawa
S
S
D000368:Aged; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000556:secondary; D017364:Collagenases / Q000032:analysis / Q000235:genetics; D018093:Gelatinases / Q000032:analysis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1; D053506:Matrix Metalloproteinase 10; D053507:Matrix Metalloproteinase 11; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000235:genetics; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011480:Protease Inhibitors / Q000032:analysis / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology*
D006023:Glycoproteins; C507096:Mmp14 protein, mouse; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D053507:Matrix Metalloproteinase 11; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D053511:Matrix Metalloproteinase 14