Abstract:Information transmission from tumor cells to non-tumor cells in the surrounding microenvironment via microvesicles is a more recently studied form of intercellular signaling that can have a marked impact on the tumor microenvironment. Tumor-derived microvesicles (TMVs) are packed with information including signaling proteins and nucleic acids, and can be taken up by target cells, enabling paracrine signaling. While previous research has focused on how vesicles released from pathologic cells differ from normal … Show more
“…Finally, given the plethora of macromolecular cargo content found within microvesicles, it is worth noting that similar to what has been described for exosomes, 22 there are likely heterogeneous pools containing distinct cargo within the total microvesicle population. 23,24 Figure 1. Common biological functions of microvesicle protein cargo identified in Vesiclepedia database.…”
The ability of cells to transmit bioactive molecules to recipient cells and the extracellular environment is a fundamental requirement for both normal physiology and disease pathogenesis. It has traditionally been thought that soluble factors released from cells were responsible for this cellular signaling but recent research has revealed a fundamental role for microvesicles in this process. Microvesicles are heterogeneous membrane-bound sacs that are shed from the surface of cells into the extracellular environment in a highly regulated process. They are shed following the selective incorporation of a host of molecular cargo including multiple types of proteins and nucleic acids. In addition to providing new insight into the etiology of complex human diseases, microvesicles also show great promise as a tool for advanced diagnosis and therapy as we move forward into a new age of personalized medicine. Here we review current status of the rapidly evolving field of microvesicle biology, highlighting critical regulatory roles for several small GTPases in the biology and biogenesis of shed microvesicles.
“…Finally, given the plethora of macromolecular cargo content found within microvesicles, it is worth noting that similar to what has been described for exosomes, 22 there are likely heterogeneous pools containing distinct cargo within the total microvesicle population. 23,24 Figure 1. Common biological functions of microvesicle protein cargo identified in Vesiclepedia database.…”
The ability of cells to transmit bioactive molecules to recipient cells and the extracellular environment is a fundamental requirement for both normal physiology and disease pathogenesis. It has traditionally been thought that soluble factors released from cells were responsible for this cellular signaling but recent research has revealed a fundamental role for microvesicles in this process. Microvesicles are heterogeneous membrane-bound sacs that are shed from the surface of cells into the extracellular environment in a highly regulated process. They are shed following the selective incorporation of a host of molecular cargo including multiple types of proteins and nucleic acids. In addition to providing new insight into the etiology of complex human diseases, microvesicles also show great promise as a tool for advanced diagnosis and therapy as we move forward into a new age of personalized medicine. Here we review current status of the rapidly evolving field of microvesicle biology, highlighting critical regulatory roles for several small GTPases in the biology and biogenesis of shed microvesicles.
“…It was demonstrated that MV participate in the regulation of target cell function. Moreover, they are involved in clotting [64,69], inflammatory [2,67], immune response [63], neogenesis [8,32,45], and carcinogenesis [3,11,50] processes. Among numerous cells being the source of MV, leukocytes are of particular interest due to the diversity of their receptor and effector functions.…”
Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a target cell, the most common mechanism of cytolysis is an exocytosis of lytic granules. However, some indirect evidence suggests that MV with CD56 phenotype and leukocyte-derived MV with various phenotypes are present in the peripheral blood plasma.This research is aimed to study the phenotype, composition and cytotoxic activity of microvesicles produced by NK cells. The analysis of receptor expression showed that MV, as well as source cells of the NK-92 cell line, had a similar CD56 molecule expression profile. The expression profile in MV differs from the same in source cells by higher CD119 and CD11b expression and by lower CD18 expression. Culturing of NK-92 cells in the presence of PMA, IL-1β, TNFα, IFNγ resulted in alterations of cell phenotypes and MV. Immunoblots revealed a change of perforin and granzyme B (GrB) in MV. The analysis of the cytotoxic activity of NK-92 cells in a natural killer in vitro assay employing K562 target cells demonstrated that MV obtained from TNFα-activated cells of the NK-92 cell line increased the cytotoxicity of the same TNFα-activated NK-92 cells regarding cytotoxicity levels. This coincides with the previously revealed increased content of GrB in MV obtained from TNFα-activated cells of the NK-92 cell line. To sum up depending on the cytokine NK-92 cells produce MV that differ in their phenotype, composition and activity. Any changes in MV composition can result in changes in their functional activity: in particular, changes can increase the cytotoxic activity of NK cells of the NK-92 cell line. Thus, besides a well-known and proved way for GrB delivery to a target cell, we can suggest an additional way – the transportation of GrB within MV.
“…Several studies revealed that TMVs transport cancerous molecules to recipient cells, which eventually contribute to tumor progression and metastasis [11][12][13][14]76] [Figure 2]. Interestingly, the transport of anti-cancer drugs out of ovarian cancer cells through their secreted EVs supported the role of EVs in cancer progression and treatment.…”
Section: Mvs: the Tiny Mediators In Intercellular Communicationmentioning
confidence: 99%
“…A reduction in cancer cell stemness was recorded by inhibiting the paracrine behavior of CAFs [ 84 ] . Conversely, TMVs have been shown to activate CAFs to improve the mobility of tumor cells, while the activated fibroblasts could secret MVs and in turn facilitate tumor progression [ 12 , 85 ] . Moreover, small GTPases and RHO-associated protein kinase, key factors in the biogenesis of MVs [ 73 ] , were found to be highly expressed in both CAFs and cancer cells [ 86 ] , which indicates the possible role of CAFs in the alteration of MVs secretion.…”
Section: The Dynamic Impact Of Mvs On Sorafenib Resistancementioning
confidence: 99%
“…However, reported resistance limits its therapeutic effects [5][6][7][8][9] . Microvesicles (MVs), functional mediators in cell-to-cell communication by transferring bioactive cargoes [10] , play an important role in tumor progression and metastasis [11][12][13][14] . Interestingly, recent studies reported that HCC-derived MVs promoted sorafenib resistance in recipient liver cancer cells by transporting cancerous cargo compared to normal liver cellderived MVs [15] .…”
Overcoming drug resistance in cancer therapies remains challenging, and the tumor microenvironment plays an important part in it. Microvesicles (MVs) are functional natural carriers of cellular information, participate in intercellular communication, and dynamically regulate the tumor microenvironment. They contribute to drug resistance by transferring functional molecules between cells. Conversely, due to their specific cell or tissue targeting ability, MVs are considered as carriers for therapeutic molecules to reverse drug resistance. Thus, in this mini-review, we aim to highlight the crucial role of MVs in cell-to-cell communication and therefore their diverse impact mainly on liver cancer progression and treatment. In addition, we summarize the possible mechanisms for sorafenib resistance (one of the main hurdles in hepatocellular carcinoma treatments) and recent advances in using MVs to reverse sorafenib resistance in liver cancer therapies. Identifying the functional role of MVs in cancer therapy might provide a new aspect for developing precise novel therapeutics in the future.
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