p11 regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells
p11 regulates extracellular plasmin production and invasiveness of HT1080 fibrosarcoma cells
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DOI：
10.1096/fj.02-0697com
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发表时间：
2003-02-01
期刊：
影响因子：
4.8
通讯作者：
Waisman, DM
中科院分区：
文献类型：
--
作者：
Choi, KS;Fogg, KD;Waisman, DM
肿瘤细胞的定义特征是其逃避邻近细胞施加的约束、侵入周围组织并转移到远处部位的能力。肿瘤细胞的这种侵袭性依赖于细胞表面蛋白酶的活化。大多数癌细胞分泌尿激酶型纤溶酶原激活剂，其将细胞结合的纤溶酶原转化为纤溶酶。在这里，我们解决的问题是否纤溶酶原结合蛋白，p11，在这一过程中发挥了重要作用。用反义方向的人p11基因转染人HT 1080纤维肉瘤细胞导致细胞表面p11蛋白的丢失，并伴随着细胞纤溶酶产生、ECM降解和细胞侵袭性的降低。转染的细胞表现出减少的肺转移灶在SCID小鼠中的发展。与此相反，HT1080细胞转染p11基因的正义方向显示增加细胞表面p11蛋白和伴随的增加，在细胞纤溶酶的生产，以及增强ECM降解和增强细胞侵袭力。p11过表达的细胞显示肺转移灶的发展增强。这些数据表明纤溶酶原受体蛋白p11的细胞外表达的变化显著影响肿瘤细胞介导的细胞周围蛋白水解。
The defining characteristic of a tumor cell is its ability to escape the constraints imposed by neighboring cells, invade the surrounding tissue, and metastasize to distant sites. This invasive property of tumor cells is dependent on activation of proteases at the cell surface. Most cancer cells secrete the urokinase-type plasminogen activator, which converts cell-bound plasminogen to plasmin. Here we address the issue of whether the plasminogen binding protein, p11, plays a significant role in this process. Transfection of human HT1080 fibrosarcoma cells with the human p11 gene in the antisense orientation resulted in a loss of p11 protein from the cell surface and concomitant decreases in cellular plasmin production, ECM degradation, and cellular invasiveness. The transfected cells demonstrated reduced development of lung metastatic foci in SCID mice. In contrast, HT1080 cells transfected with the p11 gene in the sense orientation displayed increased cell surface p11 protein and concomitant increases in cellular plasmin production, as well as enhanced ECM degradation and enhanced cellular invasiveness. The p11 overexpressing cells showed enhanced development of lung metastatic foci. These data establish that changes in the extracellular expression of the plasminogen receptor protein, p11, dramatically affect tumor cell-mediated pericellular proteolysis.