Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

Araci M. R. Rondon; Chantal Kroone; Maaike Y. Kapteijn; Henri H. Versteeg; Jeroen T. Buijs

doi:10.1055/s-0039-1687895

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2019; 45(04): 396-412
DOI: 10.1055/s-0039-1687895

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

Araci M. R. Rondon^*

¹Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

,

Chantal Kroone^*

¹Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

,

Maaike Y. Kapteijn

¹Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

,

Henri H. Versteeg^#

¹Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

,

Jeroen T. Buijs^#

¹Einthoven Laboratory for Vascular and Regenerative Medicine, Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

› Author Affiliations

Abstract

It has been long-established that cancer and thrombosis are linked, but the exact underlying pathological mechanism remains to be unraveled. As the initiator of the coagulation cascade, the transmembrane glycoprotein tissue factor (TF) has been intensely investigated for its role in cancer-associated thrombosis and cancer progression. TF expression is regulated by both specific oncogenes and environmental factors, and it is shown to regulate primary growth and metastasis formation in a variety of cancer models. In clinical studies, TF has been shown to be overexpressed in most cancer types and is strongly associated with disease progression. While TF clearly associates with cancer progression, a prominent role for TF in the development of cancer-associated thrombosis is less clear. The current concept is that cancer-associated thrombosis is associated with the secretion of tumor-derived TF-positive extracellular vesicles in certain tumor types. To date, many therapeutic strategies to target TF—both in preclinical and clinical phase—are being pursued, including targeting TF or the TF:FVIIa complex by itself or by exploiting TF as a docking molecule to deliver cytotoxic compounds to the tumor. In this review, the authors summarize the current understanding of the role of TF in both cancer progression and cancer-associated thrombosis, and discuss novel insights on TF as a therapeutic target as well as a biomarker for cancer progression and VTE.

Keywords

tissue factor - cancer - coagulation - thrombosis - venous thromboembolism

Full Text

References

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