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[Coagulation and formation of malignant effusions]
F Gieseler1, B Stelck, L-F Blume
1Onkologischer Schwerpunkt, Klinik für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Schittenhelmstr. 12, 24015 Kiel. gieseler@oncology.uni-kiel.de
Hamostaseologie
|October 17, 2007
Summary
Cancer patients with malignant effusions show tumor cell resistance linked to hyper-coagulability. Activated thrombin signaling via PAR-1 receptors contributes to this resistance, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Hematology
- Coagulation Biology
Context:
- Malignant effusions are common in cancer patients, posing treatment challenges due to high tumor cell resistance.
- Patients often exhibit hyper-coagulability, indicated by elevated d-dimers and prothrombin fragments f1.2, with high rates of thrombosis.
- The role of the coagulation system in tumor cell resistance within effusions remains incompletely understood.
Purpose:
- To investigate the hypothesis that the activated coagulation system contributes to tumor cell resistance in malignant effusions.
- To analyze the expression of thrombin receptors and the presence of coagulation factors within malignant effusions.
- To elucidate the pathophysiological mechanisms underlying malignant effusion generation.
Summary:
- Analysis of malignant effusions revealed aberrant expression of PAR-1 thrombin receptors on tumor cells.
- In vitro studies demonstrated that thrombin-induced PAR-1 activation confers dose-dependent resistance to chemotherapy (idarubicin) in leukemia cells.
- Effusions contained high levels of VEGF, tissue factor, all coagulation factors of the tissue factor pathway, and elevated prothrombin fragments f1.2, indicating ongoing thrombin generation.
Impact:
- Findings suggest that activated coagulation, particularly thrombin signaling via PAR-1, plays a significant role in chemoresistance within malignant effusions.
- Identifies a potential link between hyper-coagulability and treatment refractoriness in cancer patients with effusions.
- Provides a foundation for developing novel therapeutic strategies targeting the coagulation system to overcome chemoresistance in malignant effusions.
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