The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System

Karolina Aleksandrowicz; Dominika Hempel; Barbara Polityńska; Anna M. Wojtukiewicz; Kenneth V. Honn; Dean G. Tang; Marek Z. Wojtukiewicz

doi:10.1055/s-0043-1776875

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2024; 50(03): 462-473
DOI: 10.1055/s-0043-1776875

Review Article

The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System

Authors

Karolina Aleksandrowicz^*

¹Department of Clinical Oncology, Medical University, Białystok, Poland

²Comprehensive Cancer Center, Bialystok, Poland
Dominika Hempel^*

¹Department of Clinical Oncology, Medical University, Białystok, Poland

²Comprehensive Cancer Center, Bialystok, Poland
Barbara Polityńska

³Department of Psychology and Philosophy, Medical University of Białystok, Białystok, Poland
Anna M. Wojtukiewicz

³Department of Psychology and Philosophy, Medical University of Białystok, Białystok, Poland
Kenneth V. Honn

⁴Department of Pathology-School of Medicine, Bioactive Lipids Research Program, Detroit, Michigan

⁵Department of Chemistry, Wayne State University, Detroit, Michigan

⁶Department of Oncology, Wayne State University, Detroit, Michigan
Dean G. Tang

⁷Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York
Marek Z. Wojtukiewicz

¹Department of Clinical Oncology, Medical University, Białystok, Poland

²Comprehensive Cancer Center, Bialystok, Poland

Abstract

Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin, initiates platelet activation, and promotes clot formation. Thrombin also activates anticoagulant pathways, indirectly inhibiting factors involved in coagulation. Tissue factor triggers thrombin generation, and the overexpression of thrombin in various cancers suggests that it is involved in tumor growth, angiogenesis, and metastasis. Increased thrombin generation has been observed in cancer patients, especially those with metastases. Thrombin exerts its effects through protease-activated receptors (PARs), particularly PAR-1 and PAR-2, which are involved in cancer progression, angiogenesis, and immunological responses. Thrombin-mediated signaling promotes angiogenesis by activating endothelial cells and platelets, thereby releasing proangiogenic factors. These functions of thrombin are well recognized and have been widely described. However, in recent years, intriguing new findings concerning the association between thrombin activity and cancer development have come to light, which justifies a review of this research. In particular, there is evidence that thrombin-mediated events interact with the immune system, and may regulate its response to tumor growth. It is also worth reevaluating the impact of thrombin on thrombocytes in conjunction with its multifaceted influence on tumor progression. Understanding the role of thrombin/PAR-mediated signaling in cancer and immunological responses is crucial, particularly in the context of developing immunotherapies. In this systematic review, we focus on the impact of the thrombin-related immune system response on cancer progression.

Keywords

thrombin - neoplasm - metastasis - immune system - platelets - protease-activated receptors - neutrophil extracellular traps

Full Text

References

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