Platelet mediated cancer modulation A comprehensive review from biological mechanisms (original) (raw)
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International Journal of Molecular Sciences
Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disea...
Role of Platelets in Inflammation and Cancer: Novel Therapeutic Strategies
Basic & Clinical Pharmacology & Toxicology, 2014
Platelets 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)A 2 ] and proteins (a wide number of angiogenic and growth factors) stored in a-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)E 2 . 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 lowdose aspirin, and possibly other antiplatelet agents, in primary prevention, that is, even for individuals at low cardiovascular risk.
Multifaceted role of cancer educated platelets in survival of cancer cells
Thrombosis Research, 2019
Platelets, the derivatives of megakaryocytes, pose dynamic biological functions such as homeostasis and wound healing. The mechanisms involved in these processes are utilized by cancerous cells for proliferation and metastasis. Platelets through their activation establishes an aggregate termed as Tumor cell induced platelet aggregation (TCIPA) that aids in establishing a niche for the primary tumor at secondary site while recruiting granulocytes and monocytes. The study of these close interactions between tumor and platelets can be exploited as biomarkers in liquid biopsy for early cancer detection thereby increasing the life expectancy of cancer patients. Introduction: Platelets originate from large progenitor cells often known as megakaryocytes present in bone marrow and are abundantly found in blood (150-400 x 10 9 /L) 1. Platelets poses dynamic biological functions including hemostasis, arterial thrombosis, immunity, inflammation, vessel remodeling and angiogenesis 2 3. In this review, a novel role of platelets in liquid biopsy, has been depicted in association with oncogenesis. This study can prove to be valuable as it can help in diagnosis of early cancer development. Platelets role in tumor microenvironment The complete mechanism of action of platelets on tumor is still a mystery, yet there are evidences that suggest an interplay between platelets and tumor formation 4. In previous studies, it is suggested that platelets get activated upon recruitment to tumor microenvironment followed by secretion of certain mitogenic and angiogenic proteins from platelets that accelerates tumor proliferation 5 6. Based on the literature, a generalized model depicting interaction of platelets with primary tumor has been shown in Figure 1.
Cancer and Thrombosis: The Platelet Perspective
Frontiers in cell and developmental biology, 2016
Platelets are critical to hemostatic and immunological function, and are key players in cancer progression, metastasis, and cancer-related thrombosis. Platelets interact with immune cells to stimulate anti-tumor responses and can be activated by immune cells and tumor cells. Platelet activation can lead to complex interactions between platelets and tumor cells. Platelets facilitate cancer progression and metastasis by: (1) forming aggregates with tumor cells; (2) inducing tumor growth, epithelial-mesenchymal transition, and invasion; (3) shielding circulating tumor cells from immune surveillance and killing; (4) facilitating tethering and arrest of circulating tumor cells; and (5) promoting angiogenesis and tumor cell establishment at distant sites. Tumor cell-activated platelets also predispose cancer patients to thrombotic events. Tumor cells and tumor-derived microparticles lead to thrombosis by secreting procoagulant factors, resulting in platelet activation and clotting. Platel...
Role of platelets in cancer and cancer-associated thrombosis: Experimental and clinical evidences
Thrombosis Research, 2016
The primary hemostatic function of platelets has been recognized for more than a century, but increasing experimental and clinical evidences suggest that platelets are also important mediators of cancer. Cancer indeed influences platelet physiology, and activated platelets participate in each step of cancer development by promoting tumor growth, angiogenesis, metastasis, and cancer-associated thrombosis. Based on both the results of numerous experimental models addressing the involvement of platelets in cancer progression and the results of epidemiologic studies on the use of anti-platelet drugs to prevent cancer, platelets have been proposed as a potential target to reduce the short-term risk of cancer, cancer dissemination and cancer mortality. However, the cancer-associated thrombosis and the risk of bleeding due to anti-platelet drugs are not enough evaluated in experimental models. Therefore, the interesting contribution of platelets to cancer and cancer-associated thrombosis requires the standardization of preclinical and clinical models.
Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer
International Journal of Molecular Sciences
Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs i...
The role of platelets in tumour growth
Klinicka Onkologie Casopis Ceske a Slovenske Onkologicke Spolecnosti, 2012
Platelets, as initial responders to vascular injury, play a very important role in the initial stages of the haemostatic process. While the role of platelets in coagulation has been well studied and documented, their role in other physiological and pathological processes is just emerging. Platelets contain many biologically active molecules and, as they adhere to sites of tumour activated or injured endothelium, many of these molecules are released into the local microenvironment leading to platelet-mediated effects on vascular tone, repair and neo-angiogenesis. Platelets are likely play important roles in the tumour microenvironment that may be thought of as "a wound that never heals".
Contribution of platelets to tumour metastasis
Nature Reviews Cancer, 2011
| Extensive experimental evidence shows that platelets support tumour metastasis. The activation of platelets and the coagulation system have a crucial role in the progression of cancer. Within the circulatory system, platelets guard tumour cells from immune elimination and promote their arrest at the endothelium, supporting the establishment of secondary lesions. These contributions of platelets to tumour cell survival and spread suggest platelets as a new avenue for therapy.
Platelets Lead Morphological, Phenotypic and Functional Changes in Tumor Cells
2021
BackgroundPlatelets are active players in tumorigenesis, although the exact interactive mechanisms and their direct impact on tumor cells remain largely unknown. MethodsBidirectional transference of lipids, proteins and RNA between platelets and tumor cells and its impact on tumor cell behavior and tumor process are analyzed in this work. Phenotypic, genetic and functional modifications induced by platelets were analyzed both in tumor cell lines and in circulating tumor cells (CTCs). ResultsBesides cross-talk between platelets and tumor cells, we demonstrated an efficient exchange of lipids, proteins and RNA. Remarkably, we observed that platelets transferred structural components to tumor cells with higher efficiency than tumor cells to platelets (p=0.001). This biological interplay occurred by direct contact, internalization or via extracellular vesicles. As a result, tumor cells acquired platelet markers (CD61 and CD42), showed decreased EpCAM, expressed epithelial-to-mesenchymal...