Tsunezuka Y, Kinoh H, Takino T, Watanabe Y, Okada Y, Shinagawa A, Sato H, Seiki M
Department of Molecular Virology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Cancer Res. 1996 Dec 15;56(24):5678-83.
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.
膜型基质金属蛋白酶1（MT1-MMP）是基质金属蛋白酶（MMP）家族中最近发现的独特膜型亚组的成员。MT1-MMP对细胞外基质成分具有蛋白水解活性，并在细胞表面激活前明胶酶A（72 kDa IV型前胶原酶/前MMP-2）。由于MT1-MMP在多种肿瘤中经常表达，我们研究了其对肿瘤转移潜能的影响。将小鼠肺癌细胞系Madison 109用MT1-MMP表达质粒进行瞬时转染，并接种到BALB/c小鼠的尾静脉中。使用定量PCR方法通过质粒中的neo(r)基因监测转染细胞的命运。亲代细胞在肺中的存活率为接种细胞的0.7%。MT1-MMP转染细胞使其增加了3倍，肺结节数量也相应增加。连续组织切片的免疫染色显示，表达MT1-MMP的肺结节对明胶酶A也呈阳性，而MT1-MMP阴性细胞则完全未被明胶酶A染色。因此，表达MT1-MMP的细胞获得了结合外源性前明胶酶A的特定能力。
