Platelets Extracellular Vesicles as Regulators of Cancer Progression—An Updated Perspective

Abstract

Extracellular vesicles (EVs) are a diverse group of membrane-bound structures secreted 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. More attention is paid to assess the impact of EVs in cancer. Numerous papers showed EVs as tumorigenesis regulators, by transferring their cargo molecules (miRNA, DNA, protein, cytokines, receptors, etc.) among cancer cells and cells in the tumor microenvironment. During platelet activation or apoptosis, platelet extracellular vesicles (PEVs) are formed. PEVs present a highly heterogeneous EVs population and are the most abundant EVs group in the circulatory system. The reason for the PEVs heterogeneity are their maternal activators, which is reflected on PEVs size and cargo. As PLTs role in cancer development is well-known, and PEVs are the most numerous EVs in blood, their feasible impact on cancer growth is strongly discussed. PEVs crosstalk could promote proliferation, change tumor microenvironment, favor metastasis formation. In many cases these functions were linked to the transfer into recipient cells specific cargo molecules from PEVs. The article reviews the PEVs biogenesis, cargo molecules, and their impact on the cancer progression.

LDL-Cholesterol and Platelets: Insights into Their Interactions in Atherosclerosis

“…EVs are a diverse group of membrane-enclosed structures, released from cells to bloodstream in physiological and pathological conditions [ 55 ]. EVs act on target cells by delivering ligands and signaling complexes.…”

“…EVs act on target cells by delivering ligands and signaling complexes. For example, EVs transfer microRNAs and transcription factors that epigenetically reprogram the target cells [ 55 ]. EVs are shed by cells into the extracellular space during activation, maturation, proliferation, stress, aging, or apoptosis [ 56 ].…”

The forces driving cancer extracellular vesicle secretion

“…Compared to non-malignant cells, cancer cells have been found to increase the amount of EVs produced [18] , [19] , [20] , shift the subtype of EVs that they secrete [21] , and/or alter the cargo molecules that are selected for expulsion [ 2 , 22 , 23 ]. Of note, education by tumor cells can also affect the secretion rate and the content of EVs derived from platelets [24] , as well as noncancer cells in the TME [8] , but in this review we chose to focus on EV secretion from cancer cells only. Theoretically, both changes in content and secretion rate could contribute to the oncogenic effects of tumor-derived EVs; increased secretion of EVs with unchanged composition could drive overstimulation of recipient cells, whereas changes in EV composition, by altering EV subtype or cargo loading, could bring about tumor-supportive microenvironmental remodeling.…”

Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis

“…Recent evidence has shown that platelets can have a bimodal effect in colorectal cancer where they inhibit growth but promote metastasis [ 52 ]. An extensive review of the role of PMPs in cancer progression can be found elsewhere [ 53 ].…”