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Exosomal Lipids in Cell–Cell Communication

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Emerging Concepts of Tumor Exosome–Mediated Cell-Cell Communication

Abstract

Exosomes feature a high protein-to-lipid ratio as reported by Subra et al. [1]. However, the lipid phase and lipid mediators participate in biological activity of these vesicles. The lipid composition, membrane organization, metabolic pathways operating within exosomes, and the effects of exosomal bioactive lipids in target cells are described.

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References

  1. Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212

    Article  PubMed  CAS  Google Scholar 

  2. Record M, Subra C, Silvente-Poirot S, Poirot M (2011) Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol 81:1171–1182

    Article  PubMed  CAS  Google Scholar 

  3. Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593

    Article  PubMed  CAS  Google Scholar 

  4. Zhou L, Choi HY, Li WP, Xu F, Herz J (2009) LRP1 controls cPLA2 phosphorylation, ABCA1 expression and cellular cholesterol export. PLoS ONE 4:e6853

    Google Scholar 

  5. Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F, Pageaux JF et al (2004) Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 380:161–171

    Article  PubMed  CAS  Google Scholar 

  6. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–439

    Article  PubMed  CAS  Google Scholar 

  7. Zakharova L, Svetlova M, Fomina AF (2007) T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol 212:174–181

    Article  PubMed  CAS  Google Scholar 

  8. Blanc L, Barres C, Bette-Bobillo P, Vidal M (2007) Reticulocyte-secreted exosomes bind natural IgM antibodies: involvement of a ROS-activatable endosomal phospholipase iPLA2. Blood 110:3407–3416

    Article  PubMed  CAS  Google Scholar 

  9. Luketic L, Delanghe J, Sobol PT, Yang P, Frotten E, Mossman KL et al (2007) Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL. J Immunol 179:5024–5032

    PubMed  CAS  Google Scholar 

  10. Carayon K, Chaoui K, Ronzier E, Lazar I, Bertrand-Michel J, Roques V et al (2011) The proteo-lipidic composition of exosomes changes during reticulocyte maturation. J Biol Chem 286:34426–34439

    Article  PubMed  CAS  Google Scholar 

  11. Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J et al (2003) Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 278:10963–10972

    Article  PubMed  CAS  Google Scholar 

  12. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247

    Article  PubMed  CAS  Google Scholar 

  13. Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222

    Article  PubMed  CAS  Google Scholar 

  14. Fomina AF, Deerinck TJ, Ellisman MH, Cahalan MD (2003) Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cells. Exp Cell Res 291:150–166

    Article  PubMed  CAS  Google Scholar 

  15. Pais-Correia AM, Sachse M, Guadagnini S, Robbiati V, Lasserre R, Gessain A et al (2010) Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat Med 16:83–89

    Article  PubMed  CAS  Google Scholar 

  16. de Gassart A, Geminard C, Fevrier B, Raposo G, Vidal M (2003) Lipid raft-associated protein sorting in exosomes. Blood 102:4336–4344

    Article  PubMed  CAS  Google Scholar 

  17. Lhermusier T, Chap H, Payrastre B (2011) Platelet membrane phospholipid asymmetry: from the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J Thromb Haemost 9:1883–1891

    Article  PubMed  CAS  Google Scholar 

  18. Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294 (Pt 1):1–14

    PubMed  CAS  Google Scholar 

  19. Subra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M et al (2010) Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res 51:2105–2120

    Article  PubMed  CAS  Google Scholar 

  20. Wang D, Dubois RN (2010) Eicosanoids and cancer. Nat Rev Cancer 10:181–193

    Article  PubMed  CAS  Google Scholar 

  21. Esser J, Gehrmann U, D’Alexandri FL, Hidalgo-Estevez AM, Wheelock CE, Scheynius A et al (2010) Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol 126:1032–1040 (40 e1–4)

    Article  PubMed  CAS  Google Scholar 

  22. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  PubMed  CAS  Google Scholar 

  23. Folco G, Murphy RC (2006) Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacol Rev 58:375–388

    Article  PubMed  CAS  Google Scholar 

  24. Laulagnier K, Vincent-Schneider H, Hamdi S, Subra C, Lankar D, Record M (2005) Characterization of exosome subpopulations from RBL-2H3 cells using fluorescent lipids. Blood Cells Mol Dis 35:116–121

    Article  PubMed  CAS  Google Scholar 

  25. Foster DA (2007) Regulation of mTOR by phosphatidic acid? Cancer Res 67:1–4

    Article  PubMed  CAS  Google Scholar 

  26. Samadi N, Bekele R, Capatos D, Venkatraman G, Sariahmetoglu M, Brindley DN (2011) Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. Biochimie 93:61–70

    Article  PubMed  CAS  Google Scholar 

  27. Laulagnier K, Grand D, Dujardin A, Hamdi S, Vincent-Schneider H, Lankar D et al (2004) PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett 572:11–14

    Article  PubMed  CAS  Google Scholar 

  28. Reue K, Brindley DN (2008) Thematic review series: glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism. J Lipid Res 49:2493–2503

    Article  PubMed  CAS  Google Scholar 

  29. Alonso R, Mazzeo C, Rodriguez MC, Marsh M, Fraile-Ramos A, Calvo V et al (2011) Diacylglycerol kinase alpha regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell Death Differ 18:1161–1173

    Article  PubMed  CAS  Google Scholar 

  30. Cheng H, Sukal S, Callender R, Leyh TS (2001) gamma-phosphate protonation and pH-dependent unfolding of the Ras.GTP.Mg2 + complex: a vibrational spectroscopy study. J Biol Chem 276:9931–9935

    Article  PubMed  CAS  Google Scholar 

  31. Heo J, Gao G, Campbell SL (2004) pH-Dependent perturbation of Ras-guanine nucleotide interactions and Ras guanine nucleotide exchange. Biochemistry 43:10102–10111

    Article  CAS  Google Scholar 

  32. van Blitterswijk WJ, Hilkmann H (1993) Rapid attenuation of receptor-induced diacylglycerol and phosphatidic acid by phospholipase D-mediated transphosphatidylation: formation of bisphosphatidic acid. Embo J 12:2655–2662

    PubMed  CAS  Google Scholar 

  33. Kobayashi T, Beuchat MH, Chevallier J, Makino A, Mayran N, Escola JM et al (2002) Separation and characterization of late endosomal membrane domains. J Biol Chem 277:32157–32164

    Article  PubMed  CAS  Google Scholar 

  34. van Rossum DB, Oberdick D, Rbaibi Y, Bhardwaj G, Barrow RK, Nikolaidis N et al (2008) TRP_2, a lipid/trafficking domain that mediates diacylglycerol-induced vesicle fusion. J Biol Chem 283:34384–34392

    Article  PubMed  CAS  Google Scholar 

  35. Kobayashi T, Beuchat MH, Lindsay M, Frias S, Palmiter RD, Sakuraba H et al (1999) Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat Cell Biol 1:113–118

    Article  PubMed  CAS  Google Scholar 

  36. Delton-Vandenbroucke I, Bouvier J, Makino A, Besson N, Pageaux JF, Lagarde M et al (2007) Anti-bis(monoacylglycero)phosphate antibody accumulates acetylated LDL-derived cholesterol in cultured macrophages. J Lipid Res 48:543–552

    Article  PubMed  CAS  Google Scholar 

  37. Bouvier J, Zemski Berry KA, Hullin-Matsuda F, Makino A, Michaud S, Geloen A et al (2009) Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid. J Lipid Res 50:243–255

    Article  PubMed  CAS  Google Scholar 

  38. Chevallier J, Chamoun Z, Jiang G, Prestwich G, Sakai N, Matile S et al (2008) Lysobisphosphatidic acid controls endosomal cholesterol levels. J Biol Chem 283:27871–27880

    Article  PubMed  CAS  Google Scholar 

  39. Paillasse MR, de Medina P, Amouroux G, Mhamdi L, Poirot M, Silvente-Poirot S (2009) Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion. J Lipid Res 50:2203–2211

    Article  PubMed  CAS  Google Scholar 

  40. Mathivanan S, Fahner CJ, Reid GE, Simpson RJ (2011) ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res:1–4

    Google Scholar 

  41. Taguchi R, Ishikawa M (2010) Precise and global identification of phospholipid molecular species by an orbitrap mass spectrometer and automated search engine lipid search. J Chromatogr A 1217:4229–4239

    Article  PubMed  CAS  Google Scholar 

  42. Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF et al (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:675–687

    Article  PubMed  CAS  Google Scholar 

  43. Meyer zu Heringdorf D, Jakobs KH (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim Biophys Acta 1768:923–940

    Article  PubMed  CAS  Google Scholar 

  44. Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH (2010) TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 235:172–89

    PubMed  CAS  Google Scholar 

  45. Radu CG, Yang LV, Riedinger M, Au M, Witte ON (2004) T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci U S A 101:245–250

    Article  PubMed  CAS  Google Scholar 

  46. Perrin-Cocon L, Agaugue S, Coutant F, Masurel A, Bezzine S, Lambeau G et al (2004) Secretory phospholipase A2 induces dendritic cell maturation. Eur J Immunol 34:2293–2302

    Article  PubMed  CAS  Google Scholar 

  47. Wang D, Dubois RN (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29:781–788

    Article  PubMed  CAS  Google Scholar 

  48. Mansure JJ, Nassim R, Kassouf W (2009) Peroxisome proliferator-activated receptor gamma in bladder cancer: a promising therapeutic target. Cancer Biol Ther 8:6–15

    PubMed  Google Scholar 

  49. Skokos D, Botros HG, Demeure C, Morin J, Peronet R, Birkenmeier G et al (2003) Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol 170:3037–3045

    PubMed  CAS  Google Scholar 

  50. Lalier L, Cartron PF, Pedelaborde F, Olivier C, Loussouarn D, Martin SA et al (2007) Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients’ survival in glioblastoma multiforme. Oncogene 26:4999–5009

    Article  PubMed  CAS  Google Scholar 

  51. Chan BS, Satriano JA, Pucci M, Schuster VL (1998) Mechanism of prostaglandin E2 transport across the plasma membrane of HeLa cells and Xenopus oocytes expressing the prostaglandin transporter “PGT.” J Biol Chem 273:6689–6697

    Article  PubMed  CAS  Google Scholar 

  52. Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J et al (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124:2621–2633

    Article  PubMed  CAS  Google Scholar 

  53. Huang Q, Li F, Liu X, Li W, Shi W, Liu FF et al (2011) Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 17:860–866

    Article  PubMed  CAS  Google Scholar 

  54. Sertznig P, Seifert M, Tilgen W, Reichrath J (2007) Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. J Cell Physiol 212:1–12

    Article  PubMed  CAS  Google Scholar 

  55. Amigorena S, Savina A (2010) Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol 22:109–117

    Article  PubMed  CAS  Google Scholar 

  56. Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RR, Xu HE, Turk J et al (2009) Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. Cell 138:476–488

    Article  PubMed  CAS  Google Scholar 

  57. Bougnoux P, Hajjaji N, Maheo K, Couet C, Chevalier S (2010) Fatty acids and breast cancer: sensitization to treatments and prevention of metastatic re-growth. Prog Lipid Res 49:76–86

    Article  PubMed  CAS  Google Scholar 

  58. de Medina P, Payre B, Boubekeur N, Bertrand-Michel J, Terce F, Silvente-Poirot S et al (2009) Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism. Cell Death Differ 16:1372–1384

    Article  PubMed  CAS  Google Scholar 

  59. de Medina P, Paillasse MR, Segala G, Poirot M, Silvente-Poirot S (2010) Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands. Proc Natl Acad Sci U S A 107:13520–13525

    Article  PubMed  CAS  Google Scholar 

  60. de Medina P, Paillasse MR, Segala G, Khallouki F, Brillouet S, Dalenc F et al (2011) Importance of cholesterol and oxysterols metabolism in the pharmacology of tamoxifen and other AEBS ligands. Chem Phys Lipids 164:432–437

    Article  PubMed  CAS  Google Scholar 

  61. Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC et al (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19:1769–1779

    Article  PubMed  CAS  Google Scholar 

  62. de Medina P, Paillasse MR, Payre B, Silvente-Poirot S, Poirot M (2009) Synthesis of new alkylaminooxysterols with potent cell differentiating activities: identification of leads for the treatment of cancer and neurodegenerative diseases. J Med Chem 52:7765–7777

    Article  PubMed  CAS  Google Scholar 

  63. Silvente-Poirot S, Record M, de Medina P, Subra C, Payré B, Paillasse MR et al (2011) Dendrogenin A modifies agressive melanoma cells to secrete exosomes with antitumor activity. International Workshop on Exosomes, January 19–22, Paris, France

    Google Scholar 

  64. Wang P, Zhang Y, Li H, Chieu HK, Munn AL, Yang H (2005) AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J 24:2989–2999

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Team “Sterol Metabolism and Therapeutic Innovation in Oncology,” Cancer Research Center of Toulouse, UMR1037 INSERM-Université Toulouse, 3-CNRS ERL 5294, BP3028, CHU Purpan, 31300, Toulouse, France

    Michel Record

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Correspondence to Michel Record .

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  1. , James Brown Cancer Center, University of Louisville, 505 S. Hancock Street, Louisville, 40202, Kentucky, USA

    Huang-Ge Zhang

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Record, M. (2013). Exosomal Lipids in Cell–Cell Communication. In: Zhang, HG. (eds) Emerging Concepts of Tumor Exosome–Mediated Cell-Cell Communication. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3697-3_3

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