A MATRIX METALLOPROTEINASE EXPRESSED ON THE SURFACE OF INVASIVE TUMOR-CELLS
A MATRIX METALLOPROTEINASE EXPRESSED ON THE SURFACE OF INVASIVE TUMOR-CELLS
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DOI：
10.1038/370061a0
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发表时间：
1994-07-07
期刊：
影响因子：
64.8
通讯作者：
SEIKI, M
中科院分区：
文献类型：
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作者：
SATO, H;TAKINO, T;SEIKI, M
明胶酶A（IV型胶原酶; M（r）72，000）由肿瘤基质细胞产生，并且被认为是其侵袭和转移的关键，通过降解细胞外基质大分子如IV型胶原发挥作用（1-3）。明胶酶A的无活性前体（前明胶酶A）在侵袭性肿瘤组织中分泌并活化（4-7），这是由对金属蛋白酶抑制剂敏感的肿瘤细胞膜部分介导的蛋白水解的结果（4，5）。在这里，我们报告的互补DNA编码一种新的基质金属蛋白酶的克隆与潜在的跨膜结构域。基因产物在细胞表面上的表达在体外诱导前明胶酶A的特异性活化，并增强重建基底膜的细胞侵袭。发现含有活化形式的明胶酶A的侵袭性肺癌的肿瘤细胞表达转录物和基因产物。因此，新的金属蛋白酶可能通过激活肿瘤细胞表面的明胶酶A而引发肿瘤细胞的侵袭。
GELATINASE A (type-IV collagenase; M(r) 72,000) is produced by tumour stroma cells and is believed to be crucial for their invasion and metastasis, acting by degrading extracellular matrix macromolecules such as type IV collagen(1-3). An inactive precursor of gelatinase A (pro-gelatinase A) is secreted and activated in invasive tumour tissue(4-7) as a result of proteolysis which is mediated by a fraction of tumour cell membrane that is sensitive to metalloproteinase inhibitors(4,5). Here we report the cloning of the complementary DNA encoding a new matrix metalloproteinase with a potential transmembrane domain. Expression of the gene product on the cell surface induces specific activation of pro-gelatinase A in vitro and enhances cellular invasion of the reconstituted basement membrane. Tumour cells of invasive lung carcinomas, which contain activated forms of gelatinase A, were found to express the transcript and the gene product. The new metalloproteinase may thus trigger invasion by tumour cells by activating pro-gelatinase A on the tumour cell surface.