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Fibrinolytic system in plasma and pleural fluid in malignant pleural mesothelioma
O Ozdemir1, S Emri, Y Karakoca
1Hacettepe University Medical School, Department of Internal Medicine, Ankara, Turkey.
Abstract:
The two major fibrinolytic activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) may play role in tumor spread and metastasis. Malign pleural mesothelioma (MPM) is a kind of tumor with predominantly local invasion and low incidence of distant metastasis. In this study, u-PA, t-PA and PA activator-1 (PAI-1) antigen and activity were measured in plasma and pleural fluid samples from patients with MPM, lung cancer and benign effusion. When compared to the control group, in MPM group, plasma u-PA and t-PA antigen levels were higher, but plasma u-PA and t-PA activity were comparable. PAI-1 antigen was also higher in MPM group. These findings were in contrast to the lung cancer group, in which both activity and immunologic measurement of u-PA and t-PA were higher, but PAI-1 antigen was similar as compared to the control group. It is concluded that excess t-PA and u-PA are balanced in complexes with PAI-1 in MPM, whereas the amount of PAI-1 in plasma is insufficient to overcome the elevated t-PA and u-PA, in lung cancer. Based on these findings, it may be suggested that the balanced fibrinolytic system is responsible for the low incidence of distant metastasis in MPM.
Insights
Malignant pleural mesothelioma (MPM) shows higher levels of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) but a balanced fibrinolytic system, explaining its low distant metastasis rate.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Fibrinolytic activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA), are implicated in tumor metastasis.
- Malignant pleural mesothelioma (MPM) is characterized by local invasion and infrequent distant metastasis.
Purpose of the Study:
- To investigate the roles of u-PA, t-PA, and plasminogen activator inhibitor-1 (PAI-1) in MPM.
- To compare fibrinolytic profiles in MPM, lung cancer, and benign effusions.
Main Methods:
- Measurement of u-PA, t-PA, and PAI-1 antigen and activity in plasma and pleural fluid.
- Comparison between patients with MPM, lung cancer, and benign effusion.
Main Results:
- MPM group exhibited higher plasma u-PA and t-PA antigen levels, with comparable activity, and elevated PAI-1 antigen, compared to controls.
- Lung cancer group showed increased u-PA and t-PA activity and antigen levels, with similar PAI-1 antigen to controls.
- In MPM, excess u-PA and t-PA are balanced by PAI-1, unlike in lung cancer where PAI-1 is insufficient.
Conclusions:
- The balanced fibrinolytic system in MPM, with u-PA and t-PA complexed with PAI-1, likely contributes to the low incidence of distant metastasis.
- Differences in fibrinolytic system regulation distinguish MPM from lung cancer regarding metastatic potential.