Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M
Department of Molecular Virology and Oncology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Nature. 1994 Jul 7;370(6484):61-5. doi: 10.1038/370061a0.
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 macro-molecules such as type IV collagen. An inactive precursor of gelatinase A (pro-gelatinase A) is secreted and activated in invasive tumour tissue as a result of proteolysis which is mediated by a fraction of tumour cell membrane that is sensitive to metalloproteinase inhibitors. 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.
明胶酶A（IV型胶原酶；分子量72,000）由肿瘤基质细胞产生，据信对其侵袭和转移至关重要，通过降解细胞外基质大分子如IV型胶原发挥作用。明胶酶A的无活性前体（前明胶酶A）被分泌出来，并在侵袭性肿瘤组织中由于蛋白水解作用而被激活，这种蛋白水解作用由对金属蛋白酶抑制剂敏感的一部分肿瘤细胞膜介导。在此，我们报告了编码一种具有潜在跨膜结构域的新基质金属蛋白酶的互补DNA的克隆。基因产物在细胞表面的表达在体外诱导前明胶酶A的特异性激活，并增强重组基底膜的细胞侵袭。发现含有活化形式明胶酶A的侵袭性肺癌肿瘤细胞表达该转录本和基因产物。因此，这种新的金属蛋白酶可能通过激活肿瘤细胞表面的前明胶酶A来触发肿瘤细胞的侵袭。
