Aleksandrowicz Karolina, Hempel Dominika, Polityńska Barbara, Wojtukiewicz Anna M, Honn Kenneth V, Tang Dean G, Wojtukiewicz Marek Z
Department of Clinical Oncology, Medical University, Białystok, Poland.
Comprehensive Cancer Center, Bialystok, Poland.
Semin Thromb Hemost. 2024 Apr;50(3):462-473. doi: 10.1055/s-0043-1776875. Epub 2023 Nov 20.
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.
凝血酶是一种参与凝血过程的多效性酶，在促凝血和抗凝血途径中均发挥关键作用。凝血酶将纤维蛋白原转化为纤维蛋白，启动血小板活化，并促进血栓形成。凝血酶还激活抗凝血途径，间接抑制参与凝血的因子。组织因子触发凝血酶生成，且凝血酶在各种癌症中的过表达表明它参与肿瘤生长、血管生成和转移。在癌症患者，尤其是有转移的患者中，已观察到凝血酶生成增加。凝血酶通过蛋白酶激活受体（PARs）发挥作用，特别是PAR-1和PAR-2，它们参与癌症进展、血管生成和免疫反应。凝血酶介导的信号传导通过激活内皮细胞和血小板来促进血管生成，从而释放促血管生成因子。凝血酶的这些功能已得到充分认识并被广泛描述。然而，近年来，关于凝血酶活性与癌症发展之间关联的有趣新发现已浮出水面，这证明有必要对该研究进行综述。特别是，有证据表明凝血酶介导的事件与免疫系统相互作用，并可能调节其对肿瘤生长的反应。结合凝血酶对肿瘤进展的多方面影响，重新评估其对血小板的影响也很有必要。了解凝血酶/PAR介导的信号传导在癌症和免疫反应中的作用至关重要，尤其是在开发免疫疗法的背景下。在本系统综述中，我们重点关注凝血酶相关免疫系统反应对癌症进展的影响。
