-
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 -
Methods in Molecular Biology (Clifton,... 2013Flow cytometry is a powerful and versatile tool which can be used to provide substantial phenotypic data on platelets by yielding quantitative information of their...
Flow cytometry is a powerful and versatile tool which can be used to provide substantial phenotypic data on platelets by yielding quantitative information of their physical and antigenic properties. This includes surface expression of functional receptors, bound ligands, expression of granule components, interaction of platelets with other platelets via aggregation, or interaction with other blood components, such as leukocytes or the plasma coagulation system. Quantitative assessment of these parameters may facilitate the diagnosis of inherited or acquired platelet disorders, assist in the diagnosis of diseases associated with platelet activation, or assist in the monitoring of safety and efficacy of antiplatelet therapy.
Topics: Antibodies, Monoclonal; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Flow Cytometry; Fluorescent Antibody Technique; Humans; Immunophenotyping; Platelet Activation; Platelet Aggregation; Platelet Function Tests
PubMed: 23546718
DOI: 10.1007/978-1-62703-339-8_18 -
Cardiovascular Toxicology Feb 2020Globally, one of the major causes of death is the cardiovascular disease (CVD), and platelets play an important role in thrombosis and atherosclerosis that led to death.... (Review)
Review
Globally, one of the major causes of death is the cardiovascular disease (CVD), and platelets play an important role in thrombosis and atherosclerosis that led to death. Platelet activation can be done by different molecules, genes, pathways, and chemokines. Lipids activate platelets by inflammatory factors, and platelets are activated by receptors of peptide hormones, signaling and secreted proteins, microRNAs (miRNAs), and oxidative stress which also affect the platelet activation in older age. In addition, surface molecules on platelets can interact with other cells and chemokines in activated platelets and cause inflammation thrombosis events and CVD. However, these molecules activating platelets or being activated by platelets can be suggested as the markers to predict the clinical outcome of CVD and can be targeted to reduce thrombosis and atherosclerosis. However, hindering these molecules by other factors such as genes and receptors can reduce platelet activation and aggregation and targeting these molecules can control platelet interactions, thrombosis, and CVD. In addition, dual therapy with the receptor blockers and novel drugs results in better management of CVD patients. Overall, our review will emphasize on the molecules involved in the activation of platelets and on the molecules that are activated by platelets in CVD and discuss the molecules that can be blocked or targeted to reduce the thrombosis events and control CVD.
Topics: Animals; Blood Platelets; Cardiovascular Diseases; Humans; Molecular Targeted Therapy; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Signal Transduction
PubMed: 31784932
DOI: 10.1007/s12012-019-09555-4 -
Mass Spectrometry Reviews 2012Platelets are small cell fragments, produced by megakaryocytes, in the bone marrow. They play an important role in hemostasis and diverse thrombotic disorders. They are... (Review)
Review
Platelets are small cell fragments, produced by megakaryocytes, in the bone marrow. They play an important role in hemostasis and diverse thrombotic disorders. They are therefore primary targets of antithrombotic therapies. They are implicated in several pathophysiological pathways, such as inflammation or wound repair. In blood circulation, platelets are activated by several pathways including subendothelial matrix and thrombin, triggering the formation of the platelet plug. Studying their proteome is a powerful approach to understand their biology and function. However, particular attention must be paid to different experimental parameters, such as platelet quality and purity. Several technologies are involved during the platelet proteome processing, yielding information on protein identification, characterization, localization, and quantification. Recent technical improvements in proteomics combined with inter-disciplinary strategies, such as metabolomic, transcriptomics, and bioinformatics, will help to understand platelets biological mechanisms. Therefore, a comprehensive analysis of the platelet proteome under different environmental conditions may contribute to elucidate complex processes relevant to platelet function regarding bleeding disorders or platelet hyperreactivity and identify new targets for antiplatelet therapy.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; Proteome; Proteomics
PubMed: 22009795
DOI: 10.1002/mas.20345 -
Advances in Experimental Medicine and... 2018Platelets can be considered as the "guardian of hemostasis" where their main function is to maintain vascular integrity. In pathological conditions, the hemostatic role... (Review)
Review
Platelets can be considered as the "guardian of hemostasis" where their main function is to maintain vascular integrity. In pathological conditions, the hemostatic role of platelets may be hijacked to stimulate disease progression. In 1865, Armand Trousseau was a pioneer in establishing the platelet-cancer metastasis relationship, which he eventually termed as Trousseau's Syndrome to describe the deregulation of the hemostasis-associated pathways induced by cancer progression (Varki, Blood. 110(6):1723-9, 2007). Since these early studies, there has been an increase in experimental evidence not only to elucidate the role of platelets in cancer metastasis but also to create novel cancer therapies by targeting the platelet's impact in metastasis. In this chapter, we discuss the contribution of platelets in facilitating tumor cell transit from the primary tumor to distant metastatic sites as well as novel cancer therapies based on platelet interactions.
Topics: Blood Platelets; Drug Delivery Systems; Hemostasis; Humans; Male; Neoplasm Metastasis; Neoplasms
PubMed: 30368756
DOI: 10.1007/978-3-319-95294-9_12 -
Transfusion and Apheresis Science :... Jun 2003The roles of platelets in hemostasis and arterial thrombosis involve their adherence to sites of vessel injury or ruptured atherosclerotic plaques, aggregation to form... (Review)
Review
The roles of platelets in hemostasis and arterial thrombosis involve their adherence to sites of vessel injury or ruptured atherosclerotic plaques, aggregation to form hemostatic plugs or thrombi, and acceleration of the coagulation cascade leading to the formation of thrombin. These roles of platelets are described in this review, hereditary platelet defects and other abnormalities associated with bleeding disorders are listed, and the various aggregating agents are discussed. A number of tests of platelet function are reviewed, including a description of their advantages and disadvantages: bleeding time determination; measurement of platelet aggregation in citrated platelet-rich plasma by recording changes in light transmission; measurement of platelet aggregation in citrated whole blood by impedance aggregometry; measurement of platelet-related hemostasis with the high shear Platelet Function Analyzer (PFA-100) system and the Ultegra Rapid Platelet Function Assay; use of the Cone and Plate(let) Analyzer to measure platelet adherence and aggregation under conditions of high shear; measurement of secretion of granule contents (ATP, 14C-serotonin, platelet factor 4, beta-thromboglobulin) and the formation of thromboxane B(2); and use of flow cytometry to assess the state of platelet activation (including conformational changes in membrane glycoproteins and surface expression of P-selectin and phosphatidylserine) ex vivo and in vitro following addition of agonists, and to measure levels of platelet membrane glycoproteins in the detection of inherited deficiencies.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Platelet Aggregation; Platelet Function Tests
PubMed: 12725958
DOI: 10.1016/S1473-0502(03)00050-8 -
Current Opinion in Pharmacology Apr 2003Activation of P2Y(1) and P2Y(12) receptors, through secreted ADP that is stimulated by agonists such as thrombin, thromboxane and collagen, is a major mechanism of... (Review)
Review
Activation of P2Y(1) and P2Y(12) receptors, through secreted ADP that is stimulated by agonists such as thrombin, thromboxane and collagen, is a major mechanism of platelet activation. P2X(1) receptors also participate in platelet shape change and potentiation of calcium mobilization. The cloning of the P2Y(12) receptor and its subsequent knockout in mice promises further understanding of its downstream signaling events.
Topics: Animals; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Receptors, Purinergic
PubMed: 12681240
DOI: 10.1016/s1471-4892(03)00007-9 -
CRC Critical Reviews in Clinical... Jan 1970
Review
Topics: Animals; Antibodies; Blood Platelets; Blood Preservation; Blood Transfusion; Blood Volume Determination; Chromium Isotopes; Dimethyl Sulfoxide; Ecchymosis; Edetic Acid; Glycerol; Guinea Pigs; Humans; Megakaryocytes; Methods; Microscopy, Electron; Plasmapheresis; Platelet Adhesiveness; Thrombocytopenia
PubMed: 4999438
DOI: 10.3109/10408367009014717 -
Seminars in Thrombosis and Hemostasis Aug 2003Healthy newborns maintain normal circulating platelet counts, with a platelet ultrastructure that does not differ from adults. In vitro assessments of intrinsic platelet... (Review)
Review
Healthy newborns maintain normal circulating platelet counts, with a platelet ultrastructure that does not differ from adults. In vitro assessments of intrinsic platelet function, however, have demonstrated transient hyporesponsiveness that is most marked in platelets from preterm infants. Decreased responses were originally considered to be the result of platelet activation and degranulation during labor and delivery, but more recent studies of platelet activation markers have not supported this theory. Decreased activation responses are due to relative deficiencies of phospholipid metabolism, calcium mobilization, granule secretion, and aggregation. These result in turn from differences in intrinsic signal transduction in the neonatal platelet compared with the adult. In contrast, there is enhanced platelet adhesion due to the presence in neonatal plasma of larger, more functionally potent von Willebrand factor multimers. These ultralarge multimers may result from decreased activity of von Willebrand factor-cleaving protease in neonatal plasma and are associated with shorter bleeding times and Platelet Function Analyser-100 closure times in neonates. In the immediate newborn period, this enhanced platelet adhesion may compensate for the decreased intrinsic platelet activation in healthy neonates, but may leave sick neonates at increased risk of bleeding.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Infant, Newborn; Platelet Activation; Platelet Function Tests; Signal Transduction
PubMed: 14517748
DOI: 10.1055/s-2003-42587 -
Frontiers in Immunology 2020Platelets are small anucleate cells that are essential for many biological processes including hemostasis, thrombosis, inflammation, innate immunity, tumor metastasis,... (Review)
Review
Platelets are small anucleate cells that are essential for many biological processes including hemostasis, thrombosis, inflammation, innate immunity, tumor metastasis, and wound healing. Platelets circulate in the blood and in order to perform all of their biological roles, platelets must be able to arrest their movement at an appropriate site and time. Our knowledge of how platelets achieve this has expanded as our ability to visualize and quantify discreet platelet events has improved. Platelets are exquisitely sensitive to changes in blood flow parameters and so the visualization of rapid intricate platelet processes under conditions found in flowing blood provides a substantial challenge to the platelet imaging field. The platelet's size (~2 μm), rapid activation (milliseconds), and unsuitability for genetic manipulation, means that appropriate imaging tools are limited. However, with the application of modern imaging systems to study platelet function, our understanding of molecular events mediating platelet adhesion from a single-cell perspective, to platelet recruitment and activation, leading to thrombus (clot) formation has expanded dramatically. This review will discuss current platelet imaging techniques and , describing how the advancements in imaging have helped answer/expand on platelet biology with a particular focus on hemostasis. We will focus on platelet aggregation and thrombus formation, and how platelet imaging has enhanced our understanding of key events, highlighting the knowledge gained through the application of imaging modalities to experimental models and . Furthermore, we will review the limitations of current imaging techniques, and questions in thrombosis research that remain to be addressed. Finally, we will speculate how the same imaging advancements might be applied to the imaging of other vascular cell biological functions and visualization of dynamic cell-cell interactions.
Topics: Animals; Blood Platelets; Humans; Imaging, Three-Dimensional; Microscopy, Electron, Scanning; Optical Imaging
PubMed: 32082328
DOI: 10.3389/fimmu.2020.00078