Czekay Ralf-Peter, Loskutoff David J
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Exp Biol Med (Maywood). 2004 Dec;229(11):1090-6. doi: 10.1177/153537020422901102.
Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo, and thus it is one of the main regulators of the fibrinolytic system. In this regard, individuals with elevated PAI-1 seem to have an increased risk for thrombotic disease, whereas those lacking the inhibitor develop a lifelong bleeding diathesis. Unexpectedly, recent observations demonstrate that cancer patients with high PAI-1 levels have a poor prognosis for survival. This correlation with metastatic disease may be related to the observation that high PAI-1 levels decrease the adhesive strength of cells for their substratum, and that this de-adhesive activity of PAI-1 is not related to its role as a protease inhibitor. Initial insights into potential mechanisms by which PAI-1 regulates the attachment, detachment, and migration of cells are addressed in this review.
纤溶酶原激活物抑制剂1（PAI-1）是体内纤溶酶原激活的主要生理性抑制剂，因此它是纤维蛋白溶解系统的主要调节因子之一。在这方面，PAI-1水平升高的个体似乎患血栓性疾病的风险增加，而缺乏该抑制剂的个体则会出现终身出血倾向。出乎意料的是，最近的观察结果表明，PAI-1水平高的癌症患者生存预后较差。这种与转移性疾病的相关性可能与以下观察结果有关：高PAI-1水平会降低细胞与基质的黏附强度，并且PAI-1的这种去黏附活性与其作为蛋白酶抑制剂的作用无关。本文综述了对PAI-1调节细胞附着、脱离和迁移的潜在机制的初步见解。
