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Cancer and Platelet Crosstalk: Opportunities and challenges for aspirin and other anti-platelet agents

Xiaohong Ruby Xu, George M. Yousef and Heyu Ni

Abstract

Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis. Reciprocally, platelets reinforce tumor growth with proliferation signals, anti-apoptotic effect, and angiogenic factors. Platelets also activate tumor invasion and sustain metastasis via inducing an invasive epithelial-mesenchymal transition phenotype of tumor cells, promoting tumor survival in circulation, tumor arrest at the endothelium, and extravasation. Furthermore, platelets assist tumors in evading immune destruction. Hence, cancer cells and platelets maintain a complex, bidirectional communication. Recently, aspirin (acetylsalicylic acid) has been recognized as a promising cancer-preventative agent. It is recommended at daily low-dose by the United States Preventive Services Task Force for primary prevention of colorectal cancer. The exact mechanisms of action of aspirin in chemoprevention are not very clear, but evidence has emerged that suggests a platelet-mediated effect. In this Perspectives article, we will introduce how cancer changes platelets to be more cancer-friendly, and highlight advances in the modes of action for aspirin in cancer prevention. We also discuss the opportunities, challenges, and opposing viewpoints on applying aspirin and other anti-platelet agents for cancer prevention and treatment.

  • Submitted May 31, 2017.
  • Accepted March 4, 2018.