-
Cancer Metastasis Reviews Jun 2017Platelets play an important role in the vessel. Following their formation from megakaryocytes, platelets exist in circulation for 5-7 days and primarily function as... (Review)
Review
Platelets play an important role in the vessel. Following their formation from megakaryocytes, platelets exist in circulation for 5-7 days and primarily function as regulators of hemostasis and thrombosis. Following vascular insult or injury, platelets become activated in the blood resulting in adhesion to the exposed extracellular matrix underlying the endothelium, formation of a platelet plug, and finally formation and consolidation of a thrombus consisting of both a core and shell. In pathological conditions, platelets are essential for formation of occlusive thrombus formation and as a result are the primary target for prevention of arterial thrombus formation. In addition to regulation of hemostasis in the vessel, platelets have also been shown to play an important role in innate immunity as well as regulation of tumor growth and extravasations in the vessel. These primary functions of the platelet represent its normal function and versatility in circulation.
Topics: Animals; Blood Platelets; Hemostasis; Humans; Thrombosis
PubMed: 28667366
DOI: 10.1007/s10555-017-9677-x -
Journal of Hematology & Oncology Oct 2018The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells... (Review)
Review
The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells immediately activate platelets to form a permissive microenvironment. Platelets protect tumor cells from shear forces and assault of NK cells, recruit myeloid cells by secretion of chemokines, and mediate an arrest of the tumor cell platelet embolus at the vascular wall. Subsequently, platelet-derived growth factors confer a mesenchymal-like phenotype to tumor cells and open the capillary endothelium to expedite extravasation in distant organs. Finally, platelet-secreted growth factors stimulate tumor cell proliferation to micrometastatic foci. This review provides a synopsis on the current literature on platelet-mediated effects in cancer metastasis and particularly focuses on platelet adhesion receptors and their role in metastasis. Immunoreceptor tyrosine-based activation motif (ITAM) and hemi ITAM (hemITAM) comprising receptors, especially, glycoprotein VI (GPVI), FcγRIIa, and C-type lectin-like-2 receptor (CLEC-2) are turned in the spotlight since several new mechanisms and contributions to metastasis have been attributed to this family of platelet receptors in the last years.
Topics: Animals; Blood Platelets; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 30305116
DOI: 10.1186/s13045-018-0669-2 -
Blood Jun 2021Platelets have long been known to play important roles beyond hemostasis and thrombosis. Now recognized as a bona fide mediator of malignant disease, platelets influence... (Review)
Review
Platelets have long been known to play important roles beyond hemostasis and thrombosis. Now recognized as a bona fide mediator of malignant disease, platelets influence various aspects of cancer progression, most notably tumor cell metastasis. Interestingly, platelets isolated from cancer patients often display distinct RNA and protein profiles, with no clear alterations in hemostatic activity. This phenotypically distinct population, termed tumor-educated platelets, now receive significant attention for their potential use as a readily available liquid biopsy for early cancer detection. Although the mechanisms underpinning platelet education are still being defined, direct uptake and storage of tumor-derived factors, signal-dependent changes in platelet RNA processing, and differential platelet production by tumor-educated megakaryocytes are the most prominent scenarios. This article aims to cover the various modalities of platelet education by tumors, in addition to assessing their diagnostic potential.
Topics: Animals; Blood Platelets; Humans; Liquid Biopsy; Megakaryocytes; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; RNA, Neoplasm
PubMed: 33940594
DOI: 10.1182/blood.2019003976 -
Physiology (Bethesda, Md.) Mar 2017Upon blood vessel injury, platelets are exposed to adhesive proteins in the vascular wall and soluble agonists, which initiate platelet activation, leading to formation... (Review)
Review
Upon blood vessel injury, platelets are exposed to adhesive proteins in the vascular wall and soluble agonists, which initiate platelet activation, leading to formation of hemostatic thrombi. Pathological activation of platelets can induce occlusive thrombosis, resulting in ischemic events such as heart attack and stroke, which are leading causes of death globally. Platelet activation requires intracellular signal transduction initiated by platelet receptors for adhesion proteins and soluble agonists. Whereas many platelet activation signaling pathways have been established for many years, significant recent progress reveals much more complex and sophisticated signaling and amplification networks. With the discovery of new receptor signaling pathways and regulatory networks, some of the long-standing concepts of platelet signaling have been challenged. This review provides an overview of the new developments and concepts in platelet activation signaling.
Topics: Animals; Blood Platelets; Cyclic GMP; Humans; Inflammation; Integrins; Mice; Platelet Activation; Platelet Adhesiveness; Signal Transduction; Thrombosis
PubMed: 28228483
DOI: 10.1152/physiol.00020.2016 -
Clinical Journal of the American... Jan 2022Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying... (Review)
Review
Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.
Topics: Blood Coagulation Disorders; Blood Platelets; Humans; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic
PubMed: 34750169
DOI: 10.2215/CJN.04100321 -
Vascular Health and Risk Management 2015In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or... (Review)
Review
In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation - adhesion, shape change, release reaction, and aggregation - have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.
Topics: Animals; Blood Coagulation Disorders; Blood Platelets; Drug Monitoring; Equipment Design; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Systems; Predictive Value of Tests
PubMed: 25733843
DOI: 10.2147/VHRM.S44469 -
Pharmacological Reviews Jul 2018Platelets are essential for clotting in the blood and maintenance of normal hemostasis. Under pathologic conditions such as atherosclerosis, vascular injury often... (Review)
Review
Platelets are essential for clotting in the blood and maintenance of normal hemostasis. Under pathologic conditions such as atherosclerosis, vascular injury often results in hyperactive platelet activation, resulting in occlusive thrombus formation, myocardial infarction, and stroke. Recent work in the field has elucidated a number of platelet functions unique from that of maintaining hemostasis, including regulation of tumor growth and metastasis, inflammation, infection, and immune response. Traditional therapeutic targets for inhibiting platelet activation have primarily been limited to cyclooxygenase-1, integrin , and the P2Y receptor. Recently identified signaling pathways regulating platelet function have made it possible to develop novel approaches for pharmacological intervention in the blood to limit platelet reactivity. In this review, we cover the newly discovered roles for platelets as well as their role in hemostasis and thrombosis. These new roles for platelets lend importance to the development of new therapies targeted to the platelet. Additionally, we highlight the promising receptor and enzymatic targets that may further decrease platelet activation and help to address the myriad of pathologic conditions now known to involve platelets without significant effects on hemostasis.
Topics: Animals; Blood Platelets; Fibrinolytic Agents; Humans; Molecular Targeted Therapy; Platelet Activation; Platelet Aggregation Inhibitors; Signal Transduction; Thrombosis
PubMed: 29925522
DOI: 10.1124/pr.117.014530 -
Cancer Cell Jun 2018Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of... (Review)
Review
Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment.
Topics: Animals; Blood Platelets; Cell-Derived Microparticles; Disease Progression; Exosomes; Humans; Neoplasm Metastasis; Neoplasms; Thrombocytosis; Tumor Burden
PubMed: 29657130
DOI: 10.1016/j.ccell.2018.03.002 -
Circulation Research Jan 2018Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular... (Review)
Review
Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells. In addition to their well-described hemostatic function, platelets are active participants in the immune response to microbial organisms and foreign substances. Although incompletely understood, the immune role of platelets is a delicate balance between its pathogenic response and its regulation of thrombotic and hemostatic functions. Platelets mediate complex vascular homeostasis via specific receptors and granule release, RNA transfer, and mitochondrial secretion that subsequently regulates hemostasis and thrombosis, infection, and innate and adaptive immunity.
Topics: Adaptive Immunity; Animals; Blood Platelets; Hemostasis; Humans; Immunity, Cellular; Immunity, Innate; Inflammation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 29348254
DOI: 10.1161/CIRCRESAHA.117.310795 -
Blood Jun 2021Platelets play significant and varied roles in cancer progression, as detailed throughout this review series, via direct interactions with cancer cells and by long-range... (Review)
Review
Platelets play significant and varied roles in cancer progression, as detailed throughout this review series, via direct interactions with cancer cells and by long-range indirect interactions mediated by platelet releasates. Microvesicles (MVs; also referred to as microparticles) released from activated platelets have emerged as major contributors to the platelet-cancer nexus. Interactions of platelet-derived MVs (PMVs) with cancer cells can promote disease progression through multiple mechanisms, but PMVs also harbor antitumor functions. This complex relationship derives from PMVs' binding to both cancer cells and nontransformed cells in the tumor microenvironment and transferring platelet-derived contents to the target cell, each of which can have stimulatory or modulatory effects. MVs are extracellular vesicles of heterogeneous size, ranging from 100 nm to 1 µm in diameter, shed by living cells during the outward budding of the plasma membrane, entrapping local cytosolic contents in an apparently stochastic manner. Hence, PMVs are encapsulated by a lipid bilayer harboring surface proteins and lipids mirroring the platelet exterior, with internal components including platelet-derived mature messenger RNAs, pre-mRNAs, microRNAs, and other noncoding RNAs, proteins, second messengers, and mitochondria. Each of these elements engages in established and putative PMV functions in cancer. In addition, PMVs contribute to cancer comorbidities because of their roles in coagulation and thrombosis and via interactions with inflammatory cells. However, separating the effects of PMVs from those of platelets in cancer contexts continues to be a major hurdle. This review summarizes our emerging understanding of the complex roles of PMVs in the development and progression of cancer and cancer comorbidities.
Topics: Animals; Blood Platelets; Cell Communication; Extracellular Vesicles; Humans; Neoplasms; RNA, Neoplasm; Tumor Microenvironment
PubMed: 33940593
DOI: 10.1182/blood.2019004119