The biology of extracellular vesicles with focus on platelet microparticles and their role in cancer development and progression

Abstract

Extracellular vesicles (EVs) are a heterogeneous group of structures which can be classified into smaller in size and relatively homogenous exosomes (EXSMs)—spherical fragments of lipid bilayers from inner cell compartments—and bigger in size ectosomes (ECSMs)—a direct consequence of cell-membrane blebbing. EVs can be found in body fluids of healthy individuals. Their number increases in cancer and other pathological conditions. EVs can originate from various cell types, including leukocytes, erythrocytes, thrombocytes, and neoplastic cells. Platelet microparticles (PMPs) are the most abundant population of EVs in blood. It is well documented that PMPs, being a crucial element of EVs signaling, are involved in tumor growth, metastasis, and angiogenesis and may participate in the development of multidrug resistance by tumor cells. The aim of this review is to present the role of PMPs in carcinogenesis. The biology and functions of PMPs with a particular emphasis on the most recent scientific reports on EV properties are also characterized.

Characterization and function of medium and large extracellular vesicles from plasma and urine by surface antigens and Annexin V

“…Because triple peptidase positive m/lEVs were negative for Annexin V, the mechanism of budding from cells may not be dependent on scramblase. [25] Platelet-derived m/lEVs are the most abundant population of extracellular vesicles in blood, and their presence [11] and connection with tumor formation were reported in a recent study [29]. In our study, platelet-derived EVs were observed in healthy subjects and had the highest abundance of Annexin V-positive EVs.…”

Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

“…The formation of microparticles is a process similar to cytokinesis . It involves the disruption of the calcium‐dependent actin cytoskeleton and the proteolysis of actin bonds from plasma membrane phospholipids . This induces the membrane to bleb spontaneously because of the pressure difference .…”

“…(24) It involves the disruption of the calcium-dependent actin cytoskeleton and the proteolysis of actin bonds from plasma membrane phospholipids. (43) This induces the membrane to bleb spontaneously because of the pressure difference. (24,43) However, other mechanisms have been implicated, such as membrane curvature proteins, lipid membrane reorganization, and actin-myosin contraction elicited through guanosine triphosphate-binding protein, adenosine diphosphateribosylation factor 6, or rho-associated protein kinase 1 signaling.…”

“…(43) This induces the membrane to bleb spontaneously because of the pressure difference. (24,43) However, other mechanisms have been implicated, such as membrane curvature proteins, lipid membrane reorganization, and actin-myosin contraction elicited through guanosine triphosphate-binding protein, adenosine diphosphateribosylation factor 6, or rho-associated protein kinase 1 signaling. (19,24) It has been proposed that microparticle formation is a spontaneous and nonregulated process.…”

Physiology and pathology of extracellular vesicules

“…ВВ способны переносить разнообразные рецепто-ры (например, тромбоцитарные интегрины) на поверх-ность раковых клеток путем слияния с ними, индуци-ровать активацию киназных каскадов (например, путей митоген-активируемой протеинкиназной сигна-лизации и протеинкиназы B), стимулировать экспрес-сию металлопротеиназ матрикса и сосудистого эндо-телиального фактора роста, подавлять апоптоз, вызывать хемотаксис и способствовать появлению метастазов, а также развитию множественной лекарст-венной устойчивости (путем переноса одних мембран-ных молекул или индукции экспрессии других) [47]. Сейчас эта область исследований бурно развивается.…”