**2.3 Microvessicles**

Microvascular vesicles are derived from myriad cell types surfaces [19]. Unlike ApoEVs, which are generated via indiscriminate surface blebbing or exosomes, which are derived intracellularly within MVBs, microvesicles are formed through active interaction between cytoskeletal protein contraction and the redistribution of phospholipids. Aminophospholipid translocases closely regulate an uneven distribution of the phospholipids in the plasma membrane leading to the formation of micro-domains [30–32]. Specifically, the plasma membrane budding process is induced by translocation of phosphatidylserine to the outer-membrane

leaflet [33, 34]. The process is completed via actin–myosin interactions which cause cytoskeletal structures to contract. This ensures the release of nascent microvesicles into the extracellular space via the direct outward blebbing and breaking off of the plasma membrane [35, 36]. After blebbing, there is a distinct localization of plasma membrane lipids and proteins which informs the rigidity and curvature of the membrane [37, 38]. In addition to the redistribution of membrane lipids and proteins, there is a selective redistribution of the components of microvesicles' cargo for specific microvesicles enrichment [39]. MVs carry proteins, such as enzymes, growth factors, growth factor receptors, cytokines and chemokines. They also carry lipids, and nucleic acids, including mRNA, miRNA, ncRNA, and genomic DNA [40]. MVs have been detected in the circulation of patients with several cancers, such as lung, breast, prostate ovarian, gastric cancer and colorectal cancer [41, 42]. They have been identified to contribute to tumorigenesis, progression of cancer cells, evasion of apoptosis by tumor cells, and induction of angiogenesis. The tumor-promoting role of MV in tumor mediated exosome communication largely depends on their bioactive cargo. It is believed that the shuttling of tumor-specific proteins to the surrounding cells influence tumor growth. This is achieved through the transfer of oncogenic traits between tumor cells, which result in enhanced tumor growth, and progression [43]. MVs are recently receiving research attention as potential biomarkers because tumor cells are able to constitutively release large amounts of MVs bearing tumor-specific antigens into the bloodstream and other bodily fluids [35]. Researchers have proposed many uses of MV in cancers. Others believe that MVs can be useful for disease staging as well as evaluate the response to therapy by permitting an accurate assessment of a patient's responsiveness and personalization of treatment [44].
