Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication

Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of ‘signaling complex’, (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.

[1]  B. Østerud The role of platelets in decrypting monocyte tissue factor. , 2001, Disease-a-month : DM.

[2]  G. Grondin,et al.  Shedding of vesicular material from the cell surface of eukaryotic cells: different cellular phenomena. , 1991, Biochimica et biophysica acta.

[3]  J. Schifferli,et al.  Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. , 2004, Blood.

[4]  H. Hoogsteden,et al.  Proteomic analysis of exosomes secreted by human mesothelioma cells. , 2004, The American journal of pathology.

[5]  Anna Janowska-Wieczorek,et al.  Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer , 2005, International journal of cancer.

[6]  Michael Gnant,et al.  Impact of pretreatment thrombocytosis on survival in primary breast cancer , 2003, Thrombosis and Haemostasis.

[7]  C. Prowse,et al.  The release of prion protein from platelets during storage of apheresis platelets , 2001, Transfusion.

[8]  M. Ratajczak,et al.  Biological Significance of the Different Erythropoietic Factors Secreted by Normal Human Early Erythroid Cells , 2003, Leukemia & lymphoma.

[9]  Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions , 2000 .

[10]  J. Sixma,et al.  Activated Platelets Release Two Types of Membrane Vesicles: Microvesicles by Surface Shedding and Exosomes Derived From Exocytosis of Multivesicular Bodies and -Granules , 1999 .

[11]  M. Mesri,et al.  Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway* , 1999, The Journal of Biological Chemistry.

[12]  V. Dolo,et al.  Membrane vesicles in ovarian cancer fluids: a new potential marker. , 1999, Anticancer research.

[13]  T. Whiteside Tumour-derived exosomes or microvesicles: another mechanism of tumour escape from the host immune system? , 2005, British Journal of Cancer.

[14]  C. Prowse,et al.  The effects of leukodepletion on the generation and removal of microvesicles and prion protein in blood components , 2006, Transfusion.

[15]  A. Fonteh,et al.  Perturbations in the control of cellular arachidonic acid levels block cell growth and induce apoptosis in HL-60 cells. , 1997, Carcinogenesis.

[16]  A. Gregor,et al.  Apoptosis in human primary brain tumours: actions of arachidonic acid. , 1998, Prostaglandins, leukotrienes, and essential fatty acids.

[17]  P. Wolf The Nature and Significance of Platelet Products in Human Plasma , 1967, British journal of haematology.

[18]  M. Ratajczak,et al.  Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. , 2001, Blood.

[19]  J. Schifferli,et al.  Microparticles released by human neutrophils adhere to erythrocytes in the presence of complement. , 2005, Experimental cell research.

[20]  I. Shiojima,et al.  Sphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[21]  K. Honn,et al.  Platelets and Cancer Metastasis: More Than an Epiphenomenon , 1992, Seminars in thrombosis and hemostasis.

[22]  L. McManus,et al.  Isolation of human platelet membrane microparticles from plasma and serum , 1982 .

[23]  M. Ratajczak,et al.  Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes , 2006, Cancer Immunology, Immunotherapy.

[24]  J. Freyssinet,et al.  Cellular microparticles: a disseminated storage pool of bioactive vascular effectors , 2004, Current opinion in hematology.

[25]  P. Musiani,et al.  Polymorphonuclear Leukocyte Apoptosis Is Inhibited by Platelet-released Mediators, Role of TGFβ-1 , 2000, Thrombosis and Haemostasis.

[26]  D. Hoon,et al.  Circulating Nucleic Acids and Proteomics of Plasma/Serum: Clinical Utility , 2004, Annals of the New York Academy of Sciences.

[27]  C. Huang,et al.  Roles of phospholipid signaling in chemoattractant-induced responses. , 2000, Journal of cell science.

[28]  P. Comfurius,et al.  Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. , 2004, Biochimica et biophysica acta.

[29]  P. Collas,et al.  Reprogrammed gene expression in a somatic cell‐free extract , 2002, EMBO reports.

[30]  M. Ratajczak,et al.  Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. , 2001, Blood.

[31]  A. Schroit,et al.  Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. , 1997, Blood.

[32]  L. Horstman,et al.  Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias. , 1993, Thrombosis research.

[33]  C. Hess,et al.  Ectosomes released by human neutrophils are specialized functional units. , 1998, Journal of immunology.

[34]  A. Levine,et al.  The regulation of exosome secretion: a novel function of the p53 protein. , 2006, Cancer research.

[35]  L. Horstman,et al.  New horizons in the analysis of circulating cell-derived microparticles. , 2004, The Keio journal of medicine.

[36]  H. K. Kim,et al.  Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. , 2003, European journal of cancer.

[37]  F. Saladino,et al.  The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. , 1998, Anticancer research.

[38]  José A López,et al.  Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. , 2005, Blood.

[39]  A. Zeiher,et al.  Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure , 2001, Circulation.

[40]  B. Osterud The role of platelets in decrypting monocyte tissue factor. , 2001, Seminars in hematology.

[41]  S. Levine,et al.  Mechanisms of Soluble Cytokine Receptor Generation , 2004, The Journal of Immunology.

[42]  M. Ratajczak,et al.  Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV , 2003, AIDS.

[43]  H. Brühl,et al.  Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection , 2000, Nature Medicine.

[44]  G. Parrinello,et al.  Evaluation of Soluble Fas Ligand as a Serological Marker for Melanoma , 2002, Dermatology.

[45]  D. Pisetsky,et al.  Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases. , 2005, Arthritis and rheumatism.

[46]  G. Raposo,et al.  Exosomes: endosomal-derived vesicles shipping extracellular messages. , 2004, Current opinion in cell biology.

[47]  A. Kakkar,et al.  Platelets and cancer. , 2002, The Lancet. Oncology.

[48]  M. Herlyn,et al.  Normal human melanocyte homeostasis as a paradigm for understanding melanoma. , 2005, The journal of investigative dermatology. Symposium proceedings.

[49]  Y. Lévy,et al.  Muscle involvement in human immunodeficiency virus‐infected patients is associated with marked selenium deficiency , 1997, Muscle & nerve.

[50]  G. Raposo,et al.  Exosomes: A Bubble Ride for Prions? , 2005, Traffic.

[51]  C. Hess,et al.  Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils. , 2003, Experimental cell research.

[52]  Hans-Hermann Gerdes,et al.  Nanotubular Highways for Intercellular Organelle Transport , 2004, Science.

[53]  S. Baylin,et al.  Hematopoietic stem cells convert into liver cells within days without fusion , 2004, Nature Cell Biology.

[54]  B. Pace,et al.  Short-chain fatty acid derivatives stimulate cell proliferation and induce STAT-5 activation. , 2001, Blood.

[55]  H. Hemker,et al.  Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis". , 1996, The Journal of clinical investigation.

[56]  Y. Okada,et al.  Activation of the precursor of gelatinase A/72 kda type IV collagenase/MMP‐2 in lung carcinomas correlates with the expression of membrane‐type matrix metalloproteinase (MT‐MMP) and with lymph node metastasis , 1995, International journal of cancer.

[57]  L. Edmunds,et al.  Interaction of leukocytes with platelet microparticles derived from outdated platelet concentrates. , 1998, Thrombosis and haemostasis.

[58]  G. FitzGerald,et al.  Arachidonic Acid in Platelet Microparticles Up-regulates Cyclooxygenase-2-dependent Prostaglandin Formation via a Protein Kinase C/Mitogen-activated Protein Kinase-dependent Pathway* , 1999, The Journal of Biological Chemistry.

[59]  L. Edmunds,et al.  Measurement of Platelet Microparticles during Cardiopulmonary Bypass by Means of Captured ELISA for GPIIb/IIIa , 1998, Thrombosis and Haemostasis.

[60]  J. Rak,et al.  Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy. , 2006, Seminars in thrombosis and hemostasis.

[61]  T. Greenwalt,et al.  The how and why of exocytic vesicles , 2006, Transfusion.

[62]  Darwin J. Prockop,et al.  Mitochondrial transfer between cells can rescue aerobic respiration , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[63]  S. Eaton,et al.  Argosomes A Potential Vehicle for the Spread of Morphogens through Epithelia , 2001, Cell.

[64]  K. O'Connor,et al.  Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells , 2004, Journal of cellular and molecular medicine.

[65]  Jichun Chen,et al.  Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria. , 2004, Blood.

[66]  S. Booth,et al.  Cellular prion protein is released on exosomes from activated platelets. , 2006, Blood.

[67]  G. FitzGerald,et al.  Mechanisms of Cellular Activation by Platelet Microparticles , 1999, Thrombosis and Haemostasis.

[68]  B. Fadeel Plasma membrane alterations during apoptosis: role in corpse clearance. , 2004, Antioxidants & redox signaling.

[69]  H. Kleinman,et al.  Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. , 2002, Cancer research.

[70]  Graça Raposo,et al.  Exosomal-like vesicles are present in human blood plasma. , 2005, International immunology.

[71]  P. Ponsaerts,et al.  Modulation of cellular behavior by exogenous messenger RNA , 2006, Leukemia.

[72]  D. Brindley,et al.  Platelet-released phospholipids link haemostasis and angiogenesis. , 2001, Cardiovascular research.

[73]  A. Booth,et al.  The Trojan exosome hypothesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[74]  R. Nieuwland,et al.  Microparticles in cardiovascular diseases. , 2003, Cardiovascular research.

[75]  G. Barbarini,et al.  Incidence of dilated cardiomyopathy and detection of HIV in myocardial cells of HIV-positive patients. Gruppo Italiano per lo Studio Cardiologico dei Pazienti Affetti da AIDS. , 1998, The New England journal of medicine.

[76]  G. FitzGerald,et al.  Modulation of monocyte-endothelial cell interactions by platelet microparticles. , 1998, The Journal of clinical investigation.

[77]  G. Mack Trial set to test how stem cells heal a broken heart , 2006, Nature Medicine.

[78]  P. Sims,et al.  Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. , 1988, The Journal of biological chemistry.

[79]  D. Praticò,et al.  Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. , 2002, Experimental hematology.

[80]  Z. Darżynkiewicz,et al.  Segregation of RNA and separate packaging of DNA and RNA in apoptotic bodies during apoptosis. , 2000, Experimental cell research.

[81]  Jayoung Kim,et al.  Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. , 2005, The Journal of clinical investigation.

[82]  J. Freyssinet,et al.  Membrane microparticles: two sides of the coin. , 2005, Physiology.

[83]  J Ratajczak,et al.  Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery , 2006, Leukemia.

[84]  H. Schöler,et al.  Nuclei of Embryonic Stem Cells Reprogram Somatic Cells , 2004, Stem cells.

[85]  G. FitzGerald,et al.  Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. , 1997, The Journal of clinical investigation.

[86]  Anthony S. Fauci,et al.  Host factors and the pathogenesis of HIV-induced disease , 1996, Nature.

[87]  D. Taub,et al.  Immunologic and hematopoietic effects of CD40 stimulation after syngeneic bone marrow transplantation in mice. , 1997, The Journal of clinical investigation.

[88]  G. Raposo,et al.  Endosomes, exosomes and Trojan viruses. , 2004, Trends in microbiology.

[89]  M. Ratajczak,et al.  Bcr-abl-positive cells secrete angiogenic factors including matrix metalloproteinases and stimulate angiogenesis in vivo in Matrigel implants , 2002, Leukemia.

[90]  K. Shedden,et al.  Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. , 2003, Cancer research.