Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay.
Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MT1-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(r) gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.
Tsunezuka
Y
Y
Department of Molecular Virology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Kinoh
H
H
Takino
T
T
Watanabe
Y
Y
Okada
Y
Y
Shinagawa
A
A
Sato
H
H
Seiki
M
M
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D002448:Cell Adhesion; D005354:Fibrosarcoma / Q000201:enzymology; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); C507096:Mmp14 protein, mouse; D009363:Neoplasm Proteins; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14