Platelets at the interface of thrombosis, inflammation, and cancer

Abstract

Although once primarily recognized for its roles in hemostasis and thrombosis, the platelet has been increasingly recognized as a multipurpose cell. Indeed, circulating platelets have the ability to influence a wide range of seemingly unrelated pathophysiologic events. Here, we highlight some of the notable observations that link platelets to inflammation, reinforcing the platelet's origin from a lower vertebrate cell type with both hemostatic and immunologic roles. In addition, we consider the relevance of platelets in cancer biology by focusing on the hallmarks of cancer and the ways platelets can influence multistep development of tumors. Beyond its traditional role in hemostasis and thrombosis, the platelet's involvement in the interplay between hemostasis, thrombosis, inflammation, and cancer is likely complex, yet extremely important in each disease process. The existence of animal models of platelet dysfunction and currently used antiplatelet therapies provide a framework for understanding mechanistic insights into a wide range of pathophysiologic events. Thus, the basic scientist studying platelet function can think beyond the traditional hemostasis and thrombosis paradigms, while the practicing hematologist must appreciate platelet relevance in a wide range of disease processes.

Figure 1

Platelets and the inflammatory axis. Shown and discussed in the text are circulating platelet properties that influence the inflammatory axis. Long studied for roles in hemostasis and thrombosis, platelets interact with granulocytes, vessel walls, and pathogens, positioning them to modulate the inflammatory response via both anti-inflammatory and proinflammatory mechanisms. Future studies must consider the state of platelet activation and how this affects the inflammatory response. Antiplatelet therapies traditionally considered only for cardiovascular disease treatment also can be evaluated for their effects on inflammation.

Figure 2

Platelets and the hallmarks of cancer. The original hallmarks of cancer included 6 biologic capabilities acquired during the complex development of tumors. Highlighted and discussed in the text are circulating platelet properties that contribute to some of the hallmarks. Thus, the platelet can be viewed as a normal cell contributing to the hallmark traits and influencing the TME. Antiplatelet therapies in the realm of cancer development and progression represent a future direction likely to impact patient prognosis and outcome.