Microvesicle
[1] In multicellular organisms, microvesicles and other EVs are found both in tissues (in the interstitial space between cells) and in many types of body fluids.
Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.
Like other EVs, they have been implicated in numerous physiologic processes, including anti-tumor effects, tumor immune suppression, metastasis, tumor-stroma interactions, angiogenesis, and tissue regeneration.
Platelets play an important role in maintaining hemostasis: they promote thrombus growth, and thus they prevent loss of blood.
[16] Endothelial microparticles have been found to prevent apoptosis in recipient cells by inhibiting the p38 pathway via inactivating mitogen-activated protein kinase (MKP)-1.
This budding process involves multiple signaling pathways including the elevation of intracellular calcium and reorganization of the cell's structural scaffolding.
[19][20][21] Microvesicle budding takes place at unique locations on the cell membrane that are enriched with specific lipids and proteins reflecting their cellular origin.
After cell stimulation, including apoptosis, a subsequent cytosolic Ca2+ increase promotes the loss of phospholipid asymmetry of the plasma membrane, subsequent phosphatidylserine exposure, and a transient phospholipidic imbalance between the external leaflet at the expense of the inner leaflet, leading to budding of the plasma membrane and microvesicle release.
The identification of RNA molecules in microvesicles supports the hypothesis that they are a biological vehicle for the transfer of nucleic acids and subsequently modulate the target cell's protein synthesis.
The discovery that microvesicles may shuttle specific mRNA and miRNA suggests that this may be a new mechanism of genetic exchange between cells.
[29] These RNAs are specifically targeted to microvesicles, in some cases containing detectable levels of RNA that is not found in significant amounts in the donor cell.
This interaction ultimately leads to fusion with the target cell and release of the vesicles' components, thereby transferring bioactive molecules, lipids, genetic material, and proteins.
The transfer of microvesicle components includes specific mRNAs and proteins, contributing to the proteomic properties of target cells.
[3] After internalization of microvesicle via endocytosis, the endosome may move across the cell and fuse with the plasma membrane, a process called transcytosis.
[21] This mechanism of action can be used in processes such as antigen presentation, where MHC molecules on the surface of microvesicle can stimulate an immune response.
After the oncogenic protein is transferred, the recipient cells become transformed and show characteristic changes in the expression levels of target genes.
It is possible that transfer of other mutant oncogenes, such as HER2, may be a general mechanism by which malignant cells cause cancer growth at distant sites.
A number of reports have demonstrated that tumor-associated microvesicles release proangiogenic factors that promote endothelial cell proliferation, angiogenesis, and tumor growth.
Subsequently, the drug-containing microvesicles are released from the cell into the extracellular environment, thereby mediating resistance to chemotherapeutic agents and resulting in significantly increased tumor growth, survival, and metastasis.
[20][34] Microvesicles from various tumor types can express specific cell-surface molecules (e.g. FasL or CD95) that induce T-cell apoptosis and reduce the effectiveness of other immune cells.
Tumor-derived microvesicles often carry protein-degrading enzymes, including matrix metalloproteinase 2 (MMP-2), MMP-9, and urokinase-type plasminogen activator (uPA).
Matrix digestion can also facilitate angiogenesis, which is important for tumor growth and is induced by the horizontal transfer of RNAs from microvesicles.
Although some of these microvesicle populations occur in the blood of healthy individuals and patients, there are obvious changes in number, cellular origin, and composition in various disease states.
[44] Tumor-associated microvesicles are abundant in the blood, urine, and other body fluids of patients with cancer, and are likely involved in tumor progression.
Thus, the concentration of plasma microvesicles with molecular markers indicative of the disease state may be used as an informative blood-based biosignature for cancer.
[51][52] Conversely, microvesicles processed from a tumor cell are involved in the transport of cancer proteins and in delivering microRNA to the surrounding healthy tissue.
Microvesicles play an important role in tumor angiogenesis and in the degradation of matrix due to the presence of metalloproteases, which facilitate metastasis.
These microparticles are detectable at a high level in synovial fluid, and they promote joint inflammation by transporting proinflammatory cytokine IL-1.
[43] Additionally, circulating microvesicles can bypass the blood–brain barrier and deliver their cargo to neurons while not having an effect on muscle cells.
[32] Current research is looking into efficiently creating microvesicles synthetically, or isolating them from patient or engineered cell lines.
