INCREASED LEVELS OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) IN HUMAN BRAIN-TUMORS

Considerable interest in the roles of serine proteases and serine prot ease inhibitors (serpins) in regulating physiologic and pathologic tis sue remodeling has led to studies that indicate their critical partici pation in development and diseases of the brain. Plasminogen activator inhibitor-1 (PAI-1) is the most significant regulator of fibrinolysis in plasma, but little is known of the levels or activities of this im portant serpin in normal brain and brain tumors. For this reason, we e stimated qualitative and quantitative levels of PAI-1 in normal human brain and various brain tumors. Western-blot results indicated that a 51 kDa band recognized with polyclonal anti-PAI-1 was more prominently in metastatic and glioblastoma than in meningiomas and low-grade glio mas; normal human brain lacked any detectable band. Reverse zymography also showed high levels of PAI-1 in malignant brain tumors. The compl ex formation with I-125-urokinase demonstrated that PAI-1 complex leve ls were increased in metastatic and glioblastoma when compared with lo w-grade gliomas and meningiomas. Since PAI-1 acts as a modulator of fi brinolysis, a better understanding of the balance between serine prote ases and PAI-1 is likely to enhance our knowledge of brain tumor biolo gy.