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48 - Role of Platelets and Thrombin in Metastasis

from PART II - CLINICAL RESEARCH

Published online by Cambridge University Press:  05 June 2012

By
Boris Kobrinsky ,
Simon Karpatkin  and
David L. Green
Edited by
David Lyden ,
Danny R. Welch  and
Bethan Psaila
Boris Kobrinsky
Affiliation:
New York University School of Medicine, United States
Simon Karpatkin
Affiliation:
New York University School of Medicine, United States
David L. Green
Affiliation:
New York University School of Medicine, United States
David Lyden
Affiliation:
Weill Cornell Medical College, New York
Danny R. Welch
Affiliation:
Weill Cornell Medical College, New York
Bethan Psaila
Affiliation:
Imperial College of Medicine, London
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Summary

In response to vascular injury, platelets become adherent and undergo activation and aggregation. The formation of the primary hemostatic platelet plug occurs simultaneously with surface activation of coagulation, leading to thrombin generation and fibrin formation. Platelet function also contributes to thrombus formation in pathologic settings, leading to vascular occlusion, usually in the setting of underlying vascular disease. Platelets contain many biologically active mediators that are released upon activation, including growth factors, coagulation factors, adhesive ligands, proteases, heparanase, cytokines, chemokines, and vasoactive lipids. Other functions of platelets include a supportive role in vascular maintenance and regulation of angiogenesis, as well as putative roles in inflammation and immunity. Indeed, platelets are now linked to such diverse physiologic and pathologic processes as wound healing and tissue regeneration, response to microbial infection, inflammatory diseases, atherogenesis, tumorigenesis, and metastasis.

Platelets contribute to tumor cell metastasis by mediating tumor cell adhesion and subsequent extravasation, stabilizing platelet–tumor cell emboli in the circulation, and protecting tumor cells from the host immune system. In the tumor microenvironment, platelets become activated and may release growth factors, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, with resulting production and remodeling of the extracellular matrix and tumor angiogenesis. In this chapter, we review the role of platelets and thrombin in metastasis. We review clinical trial data with aspirin and anticoagulants in cancer and cancer prevention, and speculate on the potential effect of thrombin in unmasking tumor dormancy.

Type
Chapter
Information
Cancer Metastasis
Biologic Basis and Therapeutics
 , pp. 552 - 562
Publisher: Cambridge University Press
Print publication year: 2011

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