Production of Urokinase-Type Plasminogen Activator (u-PA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Human Brain Tumours |
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Authors: | Y Arai T Kubota T Nakagawa M Kabuto K Sato H Kobayashi |
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Institution: | (1) Department of Neurosurgery, Fukui Medical School, Fukui, Japan, JP |
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Abstract: | Summary We investigated the role of plasminogen activators (PAs) and their inhibitor (plasminogen activator inhibitor-1, PAI-1) in
human brain tumours. The amounts of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA),
and plasminogen activator inhibitor-1 (PAI-1), and the activity of u-PA and t-PA were determined by enzyme-linked immunosorbent
assay (ELISA), and u-PA and PAI-1 were immunolocalized using monoclonal antibodies in human brain tumours and normal brain
tissues. The tissues were surgically removed from 64 patients; normal brain tissue (5 cases), low-grade glioma (4 cases),
high-grade glioma (17 cases), metastatic tumour (9 cases), meningioma (benign 12 cases, malignant 6 cases), acoustic schwannoma
(11 cases). u-PA activity and u-PA and PAI-1 antigen levels were significantly elevated in malignant brain tumours (malignant
meningiomas, high-grade gliomas, and metastatic tumours) and acoustic schwannomas but very low in benign meningiomas, low-grade
gliomas and normal brain. There was no difference in t-PA antigen levels among normal and malignant tissues, however levels
of t-PA activity were markedly decreased in metastastic tumours. All malignant brain tumour tissues showed positive immunostaining
for u-PA and PAI-1, however, some tumour cells showed negative intensity while others showed strong intensity for these antibodies.
This contrasts to the homogeneous staining pattern found in acoustic schwannoma. These findings indicate that malignancy in
human brain tumours is associated with elevated levels of u-PA and PAI-1 and that an imbalance between these proteins in a
micro-enviroment contributes (ascribes) to tumour cell invasion. |
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Keywords: | : Plasminogen activators plasminogen activator inhibitor I brain tumour invasion |
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