ELEVATED LEVELS OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN MALIGNANT HUMAN BRAIN-TUMORS

The plasminogen-plasmin system has been found to modulate neoplastic s pread and angiogenesis in tumors outside the central nervous system (C NS), but there have been no quantitative studies on the invasive and v ascular tumors of the CNS. Quantitative zymography and enzyme-linked i mmunosorbent assay were used to determine the amounts of urokinase-typ e plasminogen activator (u-PA), tissue-type plasminogen activator, and plasminogen activator inhibitors type 1 and type 2 (PAI-1 and PAI-2) in benign and malignant primary brain tumors (n = 28) as well as nonne oplastic brain (n = 5). u-PA and PAI-1 antigen were undetectable in no rmal brain but significantly elevated in glioblastoma multiforme (u-PA , 2.86 +/- 3.01 ng/mg; PAI-1, 8.19 +/- 5.57 ng/mg; P < 0.001). There w as no difference, however, in tissue-type plasminogen activator antige n levels among control, benign, or malignant tissues except for a 4- t o 7-fold increase in acoustic neuroma. PAI-2 was detected at low level s in 2 of the 33 specimens. These findings indicate that malignancy in primary CNS neoplasms is associated with elevated levels of u-PA and PAI-1, supporting the role of the plasminogen-plasmin system in the pa thogenesis of CNS malignancy and as a potential biomarker and therapeu tic target.