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Regulation of fibrin deposition by malignant mesothelioma
1Department of Medicine, University of Texas Health Sciences Center at Tyler 75710, USA.
Abstract:
Malignant mesothelioma (MM) is a locally aggressive tumor that spreads by poorly understood mechanisms. Because neoplastic spread has been linked to altered fibrin turnover, we used immunohistochemistry of nine MM and three fibrous tumors of the pleura to confirm in vivo fibrin deposition and expression of selected coagulation and fibrinolytic reactants in MM. Tumor-associated fibrin was readily detectable at site of tissue invasion. Little fibrin was distributed within the tumor, but tissue factor and tissue factor pathway inhibitor, urokinase, urokinase receptor, and plasminogen activator inhibitors 1 and 2 were all detected in either epithelioid or sarcomatous areas of MM. We used the MS-1 human pleural mesothelioma cell line to determine how expression of these reactants is regulated. Fibrinolytic activity of MS-1 is mainly due to urokinase and is responsive to cytokine stimulation. Functional extrinsic activation and prothrombinase complexes assemble at the cell surface. MM express procoagulants as well as fibrinolytic reactants in vivo and in vitro that promote local fibrin formation and remodeling. Fibrin deposition occurs primarily at areas of tissue invasion and could promote local extension of this neoplasm. Sparsity of fibrin within the central portions of the tumor stroma suggests that local resorption of transitional fibrin occurs at sites of established MM.
Insights
Malignant mesothelioma (MM) involves fibrin deposition at invasion sites, suggesting a role in tumor spread. MM cells express both procoagulant and fibrinolytic factors, enabling local fibrin remodeling.
Area of Science:
- Oncology
- Hematology
- Biochemistry
Background:
- Malignant mesothelioma (MM) is a locally aggressive pleural tumor with poorly understood spread mechanisms.
- Neoplastic spread is often associated with alterations in fibrin turnover.
- Understanding fibrin's role in MM invasion is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate in vivo fibrin deposition in MM.
- To examine the expression of coagulation and fibrinolytic factors in MM.
- To elucidate the role of fibrin in MM local invasion and spread.
Main Methods:
- Immunohistochemistry was used to detect fibrin and coagulation/fibrinolytic reactants in MM tissues.
- The MS-1 human pleural mesothelioma cell line was utilized for in vitro studies.
- Analysis included assessment of tissue factor, urokinase, and plasminogen activator inhibitors.
Main Results:
- Tumor-associated fibrin was detected at sites of tissue invasion in MM.
- MM tissues expressed tissue factor, urokinase, urokinase receptor, and plasminogen activator inhibitors.
- MS-1 cells exhibited urokinase-dependent fibrinolytic activity, responsive to cytokine stimulation.
- Functional coagulation complexes assembled on the cell surface of MM cells.
Conclusions:
- MM expresses both procoagulant and fibrinolytic factors, facilitating local fibrin formation and remodeling.
- Fibrin deposition at invasion sites likely promotes local tumor extension.
- The sparse fibrin within central tumor areas suggests resorption of transitional fibrin.