Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.
Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.
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发表时间：
1992-02
期刊：
影响因子：
11.2
通讯作者：
Y. DeClerck;N. Perez;Hiroyuki Shimada;T. Boone;K. Langley;Shirley M. Taylor
中科院分区：
文献类型：
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作者：
Y. DeClerck;N. Perez;Hiroyuki Shimada;T. Boone;K. Langley;Shirley M. Taylor
金属蛋白酶及其抑制剂之间的平衡是肿瘤侵袭和转移的关键因素。下调这些蛋白酶的活性，实现了通过转染的侵袭性和转移性大鼠细胞的互补DNA的金属蛋白酶抑制剂/金属蛋白酶组织抑制剂2（MI/TIMP-2），一种新的金属蛋白酶抑制剂最近描述。（Y. A. DeClerck等人，J. Biol. Chem.，264：17445-17453，1989; W. G. Stetler-Stevenson等人，J. Biol. Chem.，264：17374-17378，1989）。在稳定转染的细胞中分泌功能性MI/TIMP-2蛋白导致金属蛋白酶活性显著降低。在表达高水平MI/TIMP-2的转染克隆中观察到裸鼠静脉注射后肺集落形成的部分抑制。四个克隆中MI/TIMP-2的产生显著降低了皮下注射后体内肿瘤生长速率。注射并完全抑制局部组织侵袭。因此，金属蛋白酶活性的下调对局部侵袭具有显著影响，并部分抑制血行转移。
The balance between levels of metalloproteinases and their corresponding inhibitors is a critical factor in tumor invasion and metastasis. Down-regulation of the activity of these proteases was achieved by transfection of invasive and metastatic rat cells with the complementary DNA for metalloproteinase inhibitor/tissue inhibitor of metalloproteinase 2 (MI/TIMP-2), a novel inhibitor of metalloproteinases recently described. (Y. A. DeClerck et al., J. Biol. Chem., 264: 17445-17453, 1989; W. G. Stetler-Stevenson et al., J. Biol. Chem., 264: 17374-17378, 1989). Secretion of functional MI/TIMP-2 protein in stably transfected cells resulted in a marked decrease in metalloproteinase activity. Partial suppression of the formation of lung colonies after i.v. injection in nude mice was observed in a transfected clone expressing high levels of MI/TIMP-2. Production of MI/TIMP-2 in four clones markedly reduced tumor growth rate in vivo after s.c. injection and completely suppressed local tissue invasion. Thus, down-regulation of metalloproteinase activity has a striking effect on local invasion and partially suppresses hematogenous metastasis.