EXPRESSION OF MEMBRANE-TYPE MATRIX METALLOPROTEINASE-1 (MT1-MMP) IN TUMOR-CELLS ENHANCES PULMONARY METASTASIS IN AN EXPERIMENTAL METASTASISASSAY

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique membrane-type subgroup in the matrix metall oproteinase (MMP) family. MT1-MMp has proteolytic activity against com ponents 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 co ntribution to their metastatic potential. The mouse lung carcinoma cel l line Madison 109 was transiently transfected with a MT1-MMP expressi on plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neo(y) gene in the plasmid using the quantitative PCR method. The survival rate of the parental c ells in lung was 0.7% of the inoculated cells. It was increased by 3-f old with the MT1-MMp transfected cells and the number of the lung nodu les increased accordingly. Immunostaining of the consecutive tissue se ctions 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 speci fic ability to bind exogenous progelatinase A.