Fibrinogen and tumor cell metastasis

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.