Cancer and Blood Diseases Institute, The Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Cancer and Blood Diseases Institute, The Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Thromb Res. 2020 Jul;191 Suppl 1:S117-S122. doi: 10.1016/S0049-3848(20)30408-4.
The last half century of cancer research has seen an explosion in our understanding of the complex interplay between cancer cells and host-derived factors critical for cancer progression. Two important host-derived arms that are part of this complex interplay are the inflammatory immune compartment and the hemostatic system. Chronic pathological inflammation is a major factor in the development of multiple common malignancies, including adenocarcinomas of the colon, pancreas, prostate and breast. Hemostatic system components have also been shown to promote cancer progression in multiple contexts. What is only recently been recognized is the link between inflammation and hemostasis in cancer progression. The hemostatic and inflammatory innate immune systems co-evolved to deal with many of the same challenges, including trauma, infections, and thermal/chemical injuries. Their co-evolution necessarily led to bidirectional cross-talk whereby inflammatory cells can activate and alter hemostasis, and hemostatic system components serve as important regulators of inflammatory processes. This cross-talk is critical for the maintenance of vascular integrity, host defense, and wound healing. However, in the context of malignancy, the interplay of these integrated host systems has the capacity to promote multiple stages of malignancy, including tumorigenesis, tumor growth and metastatic dissemination. This review focuses on the interplay of inflammatory cells with the thrombin-fibrinogen axis and protease-activated receptor-1 in cancer pathobiology. Dissecting the mechanisms by which the inflammatory and hemostatic systems cooperatively promote cancer progression will fill in critical knowledge gaps in our understanding of malignancy, and also likely reveal novel therapeutic targets to treat and/or prevent cancer.
在过去的半个世纪里，癌症研究取得了突破性进展，我们对癌细胞与宿主来源的关键促进癌症进展因素之间的复杂相互作用有了更深入的了解。宿主来源的两个重要分支参与了这种复杂的相互作用，分别是炎症免疫和止血系统。慢性病理炎症是多种常见恶性肿瘤（包括结肠癌、胰腺癌、前列腺癌和乳腺癌）发展的主要因素。止血系统成分也被证明在多种情况下促进癌症进展。最近才认识到炎症和止血在癌症进展中的联系。止血和炎症先天免疫系统共同进化，以应对许多相同的挑战，包括创伤、感染和热/化学损伤。它们的共同进化必然导致双向交叉对话，即炎症细胞可以激活和改变止血，而止血系统成分是炎症过程的重要调节剂。这种对话对于维持血管完整性、宿主防御和伤口愈合至关重要。然而，在恶性肿瘤的背景下，这些整合的宿主系统的相互作用有能力促进恶性肿瘤的多个阶段，包括肿瘤发生、肿瘤生长和转移扩散。本综述重点关注炎症细胞与凝血酶-纤维蛋白原轴和蛋白酶激活受体-1在癌症病理生物学中的相互作用。剖析炎症和止血系统协同促进癌症进展的机制将填补我们对恶性肿瘤理解的关键知识空白，并且可能揭示出治疗和/或预防癌症的新治疗靶点。
