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.

Keywords: ectosomes; exosomes; extracellular vesicles; neoplasia.

Figure 1

Extracellular vesicle biogenesis and secretion. The exosomes (EXSMs) generation begins with the membrane bulging into the lumen of the ESE. Part of them form a part of the plasma membrane (recycling endosome), others are converted into multi vesicular body (MVB). Members of the Rab family, Rab27a and Rab27b, are involved in MVB transport and fusion with cell membrane. Transmembrane protein complex SNARE enables the MVB to dock with the cell membrane that leads to release of EXSMs to extracellular space. Ectosome (ECTSM) are formed directly by cell membrane blebbing. This process is initiated with an increase in intracellular calcium that causes the activation of enzymes—floppase and scramblase and the inhibition of flippase. This causes the rearrangement of phospholipids in the cell membrane, as well as results in breaking bonds between cytoskeleton and partial degradation of actin filaments. During formation of EXSMs and ECTSMs, mRNA and miRNA that are located in cytoplasm are randomly entered.