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Fibrinogen and tumor cell metastasis.
1Division of Hematology/Oncology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, OH 45229-3039, USA.
Haemostasis
|May 7, 2002
Summary
Fibrinogen is crucial for tumor metastasis by aiding cancer cell adhesion and survival. Inhibiting thrombin also reduces metastasis, suggesting combined therapies targeting hemostatic factors could suppress cancer spread.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- Tumor cell-associated procoagulants and fibrinolytic factors suggest local thrombin and plasmin generation are vital in tumor progression.
- Fibrinogen, a target for thrombin and plasmin, implies local fibrin deposition and dissolution may influence tumor growth and dissemination.
Discussion:
- Fibrinogen deficiency significantly reduced lung metastases in experimental and spontaneous metastasis assays using Lewis lung carcinoma and B16-BL6 melanoma models.
- This reduction was not linked to altered tumor stroma formation or primary/secondary tumor growth.
- Tumor cell fate studies indicated fibrin(ogen) is essential for sustained adhesion and survival of tumor cell emboli in the lungs.
Key Insights:
- Fibrinogen deficiency markedly diminishes, but does not abolish, lung metastasis.
- The thrombin inhibitor hirudin significantly reduces metastatic potential, even in fibrinogen-deficient mice, indicating a fibrinogen-independent mechanism for thrombin's role in tumor cell dissemination.
- Fibrinogen plays a critical role in the metastatic process, particularly in tumor cell survival and adhesion within the lung vasculature.
Outlook:
- Therapeutic strategies targeting multiple hemostatic factors may offer a novel approach for suppressing metastatic disease.
- Further research into fibrinogen-independent mechanisms of thrombin in metastasis is warranted.
- Understanding the interplay between hemostasis and cancer progression can lead to more effective anti-cancer therapies.