Extracellular vesicles (EVs) are a membrane-bound structures secreted both in physiological and pathological conditions by prokaryotic and eukaryotic cells. Their role in cell-to-cell communications has been discussed for more than two decades. Numerous papers showed EVs as tumor growth regulators, by transferring their cargo (e.g.: miRNA, proteins, receptors, cytokines) into cancer cells and cells in the tumor microenvironment. Platelet extracellular vesicles (PEVs) are formed during platelet apoptosis as well as their activation. PEVs are highly heterogeneous and the most abundant EVs population in the blood. The reason for the PEVs heterogeneity are their maternal activators, which is reflected on PEVs size and cargo. As PEVs are the most numerous EVs in circulation, their feasible impact on cancer growth isstrongly discussed. PEVs crosstalk could promote cancer cells proliferation, change tumor microenvironment and favor metastasis formation. In many cases these functions were linked to the transfer into recipient cells specific cargo molecules from PEVs.
The number of research work and scientific papers that discuss the involvement of cell-derived extracellular vesicles (EVs) in multiple physiological and pathological processes has increased rapidly during the last two decades. EVs might have an influence on target cells by delivering ligands and signaling complexes, and transferring mRNA and transcription factors that cause the epigenetic reprograming of recipient cells. EVs are submicron spherical membrane bound structures, that are generated by different prokaryotic (termed as membrane vesicles) and eukaryotic cells . EVs nomenclature take into account their cellular origin and size. Their size ranges between 10 nm to 5 µm and comprises three heterogeneous populations of vesicles—exosomes (EXSMs), ectosomes (ECTSMs) also named microparticles (MPs), and apoptotic bodies (ABs) . EVs actively secreted form parental cells with a diameter of 10 to 100 nm are named EXSMs, and those with a diameter ranging between 100 nm to 1 µm are ECTSMs. Lipid bilayer membrane protects their cargo from enzymes like proteases and ribonucleases . The largest of EVs are ABs (with diameter 1–5 µm) represented by clumps of material generated during the late stage of cell apoptosis .
During activation, maturation, proliferation, stress, aging, or apoptosis, cells shed EVs into the extracellular space . Their presence in a number of body fluids including—urine, synovial fluid, bronchoalveolar lavage fluid, saliva, and bile was confirmed . In the bloodstream, EVs are released by—erythrocytes, leukocytes, platelets (PEVs), megakaryocytes, and endothelial cells . In addition, EVs are also secreted by cancer cells known as tumor-derived extracellular vesicles (TEVs) . In both healthy subjects and those with a variety of pathologies, peripheral blood is a rich source of EVs, where the most abundant population are PEVs. Their percentage ranges between 70 to 90% of all EVs in the plasma of healthy individuals .
In 1967, Peter Wolf described “platelet dust”—a subcellular material derived from thrombocytes in the plasma and serum of healthy individuals . This was a milestone in medicine research, allowing further examinations evaluating PEVs involvement in physiological and pathological processes. PEVs share many functional features with PLTs. These tiny fragments smaller than platelets (PLTs) were secreted during PLT activation and were known to be crucial in coagulation and clot formation . Despite the fact that PLTs play a crucial role in hemostasis, PEVs coagulation capacity is several dozen higher than PLTs . Platelets microparticles (PMPs) are enriched in tissue factor (TF), coagulation factors, and dozens of them expose about 3-fold higher phosphatidylserine (PS) concentration on the outer membrane than PLTs . The coagulation process initiated by TF connection with coagulation factor VII, activates coagulation cascade. Activated PLTs, PMPs PS + offer a catalytic surface for the coagulation and binding of consecutive clotting factors. Moreover, in healthy individuals, the presence of integrin αIIbβ3 (CD41/CD61) on PMPs supports fibrin clot formation . In various bleeding disorders, abnormalities in PMPs functions and their reduced number in blood were reported . On the other hand, their increased amount was presented in thrombotic state and other pathologies . PLTs of patients described by Castaman are unable to shed PMPs, conversely to patients with Scott syndrome in which the PMPs number is adequate, but the incorrect translocation of PS impairs prothrombinase activity, and causes hemorrhagic diathesis . Patients with immune thrombocytopenia have higher PEVs level than healthy individuals, which might be an evolutionary way to prevent blood loss and maintain tissue integrity . Additionally, contemporary papers showed that PEVs might be a potential biomarker or prognostic factor in other pathologies—inflammatory, cardiovascular, and autoimmune diseases, solid tumors and hematological malignancies .
PEVs biogenesis depends on different signals that control their formation from PLTs. The role of PEVs in various physiological conditions, like hemostasis, or pathological like inflammation or atherosclerosis was confirmed. This review focused on the PEVs participation in cancerogenesis. A better understanding of the biology of PEVs and the mechanisms that allow them to function as mediators in cell-to-cell communication in cancer growth, could become a contribution to the development of new therapeutic strategies, which could also be applicable in cancer. Moreover, determining the number of PEVs and their cargo becomes a useful diagnostic marker or prognostic factor for the different clinical stages in a variety of neoplasia. Knowledge about the formation of distinct PEVs types dependent on PLTs activators could lead to the development of specific techniques for PEVs-mediated drug delivery to cancer cells, or to TME, to modulate their immune response or angiogenesis.