Role of Platelets in Inflammation and Cancer: Novel Therapeutic Strategies

Basic and Clinical Pharmacology and Toxicology - Tập 114 Số 1 - Trang 118-127 - 2014
Melania Dovizio1, Sara Alberti1, Paloma Guillem‐Llobat1, Paola Patrignani1
1Department of Neuroscience and Imaging, Section of Cardiovascular and Pharmacological Sciences, and Center of Excellence on Aging (CeSI), G. d'Annunzio University, Chieti, Italy.

Tóm tắt

AbstractPlatelets play a central role in inflammation through their direct interaction with other cell types, such as leucocytes and endothelial cells, and by the release of many factors, that is, lipids [such as thromboxane (TX)A2] and proteins (a wide number of angiogenic and growth factors) stored in α‐granules, and adenosine diphosphate (ADP), stored in dense granules. These platelet actions trigger autocrine and paracrine activation processes that lead to leucocyte recruitment into different tissues and phenotypic changes in stromal cells which contribute to the development of different disease states, such as atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The signals induced by platelets may cause pro‐inflammatory and malignant phenotypes in other cells through the persistent induction of aberrant expression of cyclooxygenase (COX)‐2 and increased generation of prostanoids, mainly prostaglandin (PG)E2. In addition to cardiovascular disease, enhanced platelet activation has been detected in inflammatory disease and intestinal tumourigenesis. Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer. All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigenesis) and endothelial (in tumourigenesis and atherothrombosis) injury. Extensive translational medicine research is necessary to obtain a definitive mechanistic demonstration of the platelet‐mediated hypothesis of colon tumourigenesis. The results of these studies will be fundamental to support the clinical decision to recommend the use of low‐dose aspirin, and possibly other antiplatelet agents, in primary prevention, that is, even for individuals at low cardiovascular risk.

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Basic and Clinical Pharmacology and Toxicology

Tập 114 Số 1

118-127

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