Landau B J, Kwaan H C, Verrusio E N, Brem S S
Division of Neurological Surgery, Northwestern University School of Medicine, Chicago, Illinois 60611-2906.
Cancer Res. 1994 Feb 15;54(4):1105-8.
The plasminogen-plasmin system has been found to modulate neoplastic spread and angiogenesis in tumors outside the central nervous system (CNS), but there have been no quantitative studies on the invasive and vascular tumors of the CNS. Quantitative zymography and enzyme-linked immunosorbent assay were used to determine the amounts of urokinase-type 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 nonneoplastic brain (n = 5). u-PA and PAI-1 antigen were undetectable in normal 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 was no difference, however, in tissue-type plasminogen activator antigen levels among control, benign, or malignant tissues except for a 4- to 7-fold increase in acoustic neuroma. PAI-2 was detected at low levels 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 pathogenesis of CNS malignancy and as a potential biomarker and therapeutic target.
纤溶酶原-纤溶酶系统已被发现可调节中枢神经系统（CNS）以外肿瘤的肿瘤扩散和血管生成，但尚未对CNS的侵袭性和血管性肿瘤进行定量研究。采用定量酶谱法和酶联免疫吸附测定法，测定28例良性和恶性原发性脑肿瘤以及5例非肿瘤性脑标本中尿激酶型纤溶酶原激活物（u-PA）、组织型纤溶酶原激活物、纤溶酶原激活物抑制剂1型和2型（PAI-1和PAI-2）的含量。正常脑中未检测到u-PA和PAI-1抗原，但在多形性胶质母细胞瘤中显著升高（u-PA，2.86±3.01 ng/mg；PAI-1，8.19±5.57 ng/mg；P<0.001）。然而，除听神经瘤中组织型纤溶酶原激活物抗原水平增加4至7倍外，对照、良性或恶性组织之间的组织型纤溶酶原激活物抗原水平无差异。33例标本中有2例检测到低水平的PAI-2。这些发现表明，原发性CNS肿瘤的恶性程度与u-PA和PAI-1水平升高有关，支持纤溶酶原-纤溶酶系统在CNS恶性肿瘤发病机制中的作用，并作为潜在的生物标志物和治疗靶点。
