Maspin inhibits cell migration in the absence of protease inhibitory activity
Maspin inhibits cell migration in the absence of protease inhibitory activity
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DOI：
10.1074/jbc.c200532200
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发表时间：
2002-12-06
影响因子：
4.8
通讯作者：
Ellis, V
中科院分区：
文献类型：
--
作者：
Bass, R;Fernández, AMM;Ellis, V
Maspin是蛋白酶抑制剂丝氨酸蛋白酶抑制剂家族的成员，是作用于肿瘤侵袭和转移水平的抑癌基因。这种体内活性与 maspin 抑制体外细胞迁移的能力相关。这种行为表明，maspin 以与丝氨酸蛋白酶抑制剂 PAI-1 类似的方式抑制基质降解蛋白酶，例如纤溶酶原激活系统的蛋白酶。然而，关于maspin的蛋白酶抑制活性存在争议。与其他非抑制性丝氨酸蛋白酶抑制剂一样，它对多种蛋白酶缺乏活性，但最近据报道可以抑制与细胞和其他生物表面相关的纤溶酶原激活剂（Sheng, S. J.、Truong, B.、Fredrickson, D.、Wit, R. L.、Pardee, A. B. 和 Sager, R. (1998) Proc. Natl. Acad. Sci. U. S. 95， 499-504； McGowen, R.、Biliran, H., Jr.、Sager, R. 和 Shen, S. (2000) 癌症研究。 60、4771-4778）。我们比较了 maspin 与 PAI-1 在纤溶酶原激活增强的一系列情况下的作用，反映了该蛋白水解系统的生物学背景：尿激酶型纤溶酶原激活剂与其肿瘤细胞表面的受体结合，组织型纤溶酶原激活剂与血管平滑肌细胞、纤维蛋白和朊病毒蛋白特异性结合。与 PAI-1 观察到的有效抑制相反，Maspin 在任何这些情况下都没有抑制作用，但 Maspin 仍然抑制肿瘤和血管平滑肌细胞的迁移。我们得出的结论是，maspin 是一种非抑制性丝氨酸蛋白酶抑制剂，蛋白酶抑制不能解释其作为肿瘤抑制因子的活性。
Maspin is a member of the serpin family of protease inhibitors and is a tumor suppressor gene acting at the level of tumor invasion and metastasis. This in vivo activity correlates with the ability of maspin to inhibit cell migration in vitro. This behavior suggests that maspin inhibits matrix-degrading proteases, such as those of the plasminogen activation system, in a similar manner to the serpin PAI-1. However, there is controversy concerning the protease inhibitory activity of maspin. It is devoid of activity against a wide range of proteases, in common with other non-inhibitory serpins, but has recently been reported to inhibit plasminogen activators associated with cells and other biological surfaces (Sheng, S. J., Truong, B., Fredrickson, D., Wit, R. L., Pardee, A. B., and Sager, R. (1998) Proc. Natl. Acad. Sci. U. S. A 95, 499-504; McGowen, R., Biliran, H., Jr., Sager, R., and Sheng, S. (2000) Cancer Res. 60, 4771-4778). We have compared the effects of maspin with those of PAI-1 in a range of situations in which plasminogen activation is potentiated, reflecting the biological context of this proteolytic system: urokinase-type plasminogen activator bound to its receptor on the surface of tumor cells, tissue-type plasminogen activator specifically bound to vascular smooth muscle cells, fibrin, and the prion protein. Maspin was found to have no inhibitory effect in any of these situations, in contrast to the efficient inhibition observed with PAI-1, but nevertheless maspin inhibited the migration of both tumor and vascular smooth muscle cells. We conclude that maspin is a non-inhibitory serpin and that protease inhibition does not account for its activity as a tumor suppressor.