Nothing Special   »   [go: up one dir, main page]
Skip to main content
Springer Nature Link
Log in

Microvesicles as Mediators of Intercellular Communication in Cancer

  • Protocol
  • First Online:
Cancer Cell Signaling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1165))

Abstract

The discovery that cancer cells generate large membrane-enclosed packets of epigenetic information, known as microvesicles (MVs), that can be transferred to other cells and influence their behavior (Antonyak et al., Small GTPases 3:219–224, 2012; Cocucci et al., Trends Cell Biol 19:43–51, 2009; Rak, Semin Thromb Hemost 36:888–906, 2010; Skog et al., Nat Cell Biol 10:1470–1476, 2008) has added a unique perspective to the classical paracrine signaling paradigm. This is largely because, in addition to growth factors and cytokines, MVs contain a variety of components that are not usually thought to be released into the extracellular environment by viable cells including plasma membrane-associated proteins, cytosolic- and nuclear-localized proteins, as well as nucleic acids, particularly RNA transcripts and micro-RNAs (Skog et al., Nat Cell Biol 10:1470–1476, 2008; Al-Nedawi et al., Nat Cell Biol 10:619–624, 2008; Antonyak et al., Proc Natl Acad Sci U S A 108:4852–4857, 2011; Balaj et al., Nat Commun 2:180, 2011; Choi et al., J Proteome Res 6:4646–4655, 2007; Del Conde et al., Blood 106:1604–1611, 2005; Gallo et al., PLoS One 7:e30679, 2012; Graner et al., FASEB J 23:1541–1557, 2009; Grange et al., Cancer Res 71:5346–5356, 2011; Hosseini-Beheshti et al., Mol Cell Proteomics 11:863–885, 2012; Martins et al., Curr Opin Oncol 25:66–75, 2013; Noerholm et al., BMC Cancer 12:22, 2012; Zhuang et al., EMBO J 31:3513–3523, 2012). When transferred between cancer cells, MVs have been shown to stimulate signaling events that promote cell growth and survival (Al-Nedawi et al., Nat Cell Biol 10:619–624, 2008). Cancer cell-derived MVs can also be taken up by normal cell types that surround the tumor, an outcome that helps shape the tumor microenvironment, trigger tumor vascularization, and even confer upon normal recipient cells the transformed characteristics of a cancer cell (Antonyak et al., Proc Natl Acad Sci U S A 108:4852–4857, 2011; Martins et al., Curr Opin Oncol 25:66–75, 2013; Al-Nedawi et al., Proc Natl Acad Sci U S A 106:3794–3799, 2009; Ge et al., Cancer Microenviron 5:323–332, 2012). Thus, the production of MVs by cancer cells plays crucial roles in driving the expansion of the primary tumor. However, it is now becoming increasingly clear that MVs are also stable in the circulation of cancer patients, where they can mediate long-range effects and contribute to the formation of the pre-metastatic niche, an essential step in metastasis (Skog et al., Nat Cell Biol 10:1470–1476, 2008; Noerholm et al., BMC Cancer 12:22, 2012; Peinado et al., Nat Med 18:883–891, 2012; Piccin et al., Blood Rev 21:157–171, 2007; van der Vos et al., Cell Mol Neurobiol 31:949–959, 2011). These findings, when taken together with the fact that MVs are being aggressively pursued as diagnostic markers, as well as being considered as potential targets for intervention against cancer (Antonyak et al., Small GTPases 3:219–224, 2012; Hosseini-Beheshti et al., Mol Cell Proteomics 11:863–885, 2012; Martins et al., Curr Opin Oncol 25:66–75, 2013; Ge et al., Cancer Microenviron 5:323–332, 2012; Peinado et al., Nat Med 18:883–891, 2012; Piccin et al., Blood Rev 21:157–171, 2007; Al-Nedawi et al., Cell Cycle 8:2014–2018, 2009; Cocucci and Meldolesi, Curr Biol 21:R940–R941, 2011; D’Souza-Schorey and Clancy, Genes Dev 26:1287–1299, 2012; Shao et al., Nat Med 18:1835–1840, 2012), point to critically important roles for MVs in human cancer progression that can potentially be exploited to develop new targeted approaches for treating this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Baraniak PR, McDevitt TC (2010) Stem cell paracrine actions and tissue regeneration. Regen Med 5:121–143

    PubMed Central  PubMed  Google Scholar 

  2. Perrimon N, Pitsouli C, Shilo BZ (2012) Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb Perspect Biol 4:a005975

    PubMed Central  PubMed  Google Scholar 

  3. Wilson KJ, Mill C, Lambert S et al (2012) EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling. Growth Factors 30:107–116

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Seshacharyulu P, Ponnusamy MP, Haridas D et al (2012) Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 16:15–31

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Shilo BZ (2005) Regulating the dynamics of EGF receptor signaling in space and time. Development 132:4017–4027

    CAS  PubMed  Google Scholar 

  6. Han W, Lo HW (2012) Landscape of EGFR signaling network in human cancers: biology and therapeutic response in relation to receptor subcellular locations. Cancer Lett 318: 124–134

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Hopkins S, Linderoth E, Hantschel O et al (2012) Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis. Dev Cell 23:547–559

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Moscatello DK, Montgomery RB, Sundareshan P et al (1996) Transformational and altered signal transduction by a naturally occurring mutant EGF receptor. Oncogene 13:85–96

    CAS  PubMed  Google Scholar 

  9. Moscatello DK, Ramirez G, Wong AJ (1997) A naturally occurring mutant human epidermal growth factor receptor as a target for peptide vaccine immunotherapy of tumors. Cancer Res 57:1419–1424

    CAS  PubMed  Google Scholar 

  10. Miettinen PJ, Berger JE, Meneses J et al (1995) Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376:337–341

    CAS  PubMed  Google Scholar 

  11. Miettinen PJ, Chin JR, Shum L et al (1999) Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. Nat Genet 22:69–73

    CAS  PubMed  Google Scholar 

  12. Threadgill DW, Dlugosz AA, Hansen LA et al (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269:230–234

    CAS  PubMed  Google Scholar 

  13. Kramer C, Klasmeyer K, Bojar H et al (2007) Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcome. Cancer 109:2016–2024

    CAS  PubMed  Google Scholar 

  14. Moscatello DK, Holgado-Madruga M, Godwin AK et al (1995) Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res 55:5536–5539

    CAS  PubMed  Google Scholar 

  15. Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    CAS  PubMed  Google Scholar 

  16. Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Antonyak MA, Kenyon LC, Godwin AK et al (2002) Elevated JNK activation contributes to the pathogenesis of human brain tumors. Oncogene 21:5038–5046

    CAS  PubMed  Google Scholar 

  18. Boroughs LK, Antonyak MA, Johnson JL et al (2011) A unique role for heat shock protein 70 and its binding partner tissue transglutaminase in cancer cell migration. J Biol Chem 286:37094–37107

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Antonyak MA, Wilson KF, Cerione RA (2012) R(h)oads to microvesicles. Small GTPases 3:219–224

    PubMed Central  PubMed  Google Scholar 

  20. Al-Nedawi K, Meehan B, Rak J (2009) Microvesicles: messengers and mediators of tumor progression. Cell Cycle 8:2014–2018

    CAS  PubMed  Google Scholar 

  21. Cocucci E, Meldolesi J (2011) Ectosomes. Curr Biol 21:R940–R941

    CAS  PubMed  Google Scholar 

  22. D’Souza-Schorey C, Clancy JW (2012) Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev 26:1287–1299

    PubMed Central  PubMed  Google Scholar 

  23. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51

    CAS  PubMed  Google Scholar 

  24. Di Vizio D, Kim J, Hager MH et al (2009) Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res 69:5601–5609

    PubMed Central  PubMed  Google Scholar 

  25. Varon D, Shai E (2009) Role of platelet-derived microparticles in angiogenesis and tumor progression. Discov Med 8:237–241

    PubMed  Google Scholar 

  26. Skog J, Wurdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Al-Nedawi K, Meehan B, Micallef J et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624

    CAS  PubMed  Google Scholar 

  28. Al-Nedawi K, Meehan B, Kerbel RS et al (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A 106:3794–3799

    PubMed Central  PubMed  Google Scholar 

  29. van der Vos KE, Balaj L, Skog J et al (2011) Brain tumor microvesicles: insights into intercellular communication in the nervous system. Cell Mol Neurobiol 31:949–959

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Wysoczynski M, Ratajczak MZ (2009) Lung cancer secreted microvesicles: underappreciated modulators of microenvironment in expanding tumors. Int J Cancer 125:1595–1603

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Antonyak MA, Li B, Boroughs LK et al (2011) Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc Natl Acad Sci U S A 108:4852–4857

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Tian T, Wang Y, Wang H et al (2010) Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. J Cell Biochem 111:488–496

    CAS  PubMed  Google Scholar 

  33. Rak J (2010) Microparticles in cancer. Semin Thromb Hemost 36:888–906

    CAS  PubMed  Google Scholar 

  34. Ge R, Tan E, Sharghi-Namini S et al (2012) Exosomes in cancer microenvironment and beyond: have we overlooked these extracellular messengers? Cancer Microenviron 5:323–332

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Di Vizio D, Morello M, Dudley AC et al (2012) Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol 181:1573–1584

    PubMed Central  PubMed  Google Scholar 

  36. Ginestra A, La Placa MD, Saladino F et al (1998) The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. Anticancer Res 18:3433–3437

    CAS  PubMed  Google Scholar 

  37. Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920

    CAS  PubMed  Google Scholar 

  38. Teis D, Saksena S, Emr SD (2009) SnapShot: the ESCRT machinery. Cell 137:182–182 e181

    Google Scholar 

  39. Ceruti S, Colombo L, Magni G et al (2011) Oxygen-glucose deprivation increases the enzymatic activity and the microvesicle-mediated release of ectonucleotidases in the cells composing the blood–brain barrier. Neurochem Int 59:259–271

    CAS  PubMed  Google Scholar 

  40. Hanson PI, Cashikar A (2012) Multivesicular body morphogenesis. Annu Rev Cell Dev Biol 28:337–362

    CAS  PubMed  Google Scholar 

  41. Piccin A, Murphy WG, Smith OP (2007) Circulating microparticles: pathophysiology and clinical implications. Blood Rev 21:157–171

    CAS  PubMed  Google Scholar 

  42. Muralidharan-Chari V, Clancy JW, Sedgwick A et al (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Muralidharan-Chari V, Clancy J, Plou C et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19:1875–1885

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Hosseini-Beheshti E, Pham S, Adomat H et al (2012) Exosomes as biomarker enriched microvesicles: characterization of exosomal proteins derived from a panel of prostate cell lines with distinct AR phenotypes. Mol Cell Proteomics 11:863–885

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Li B, Antonyak MA, Zhang J et al (2012) RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31:4740–4749

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Scott G (2012) Demonstration of melanosome transfer by a shedding microvesicle mechanism. J Invest Dermatol 132:1073–1074

    CAS  PubMed  Google Scholar 

  47. Shen B, Wu N, Yang JM et al (2011) Protein targeting to exosomes/microvesicles by plasma membrane anchors. J Biol Chem 286:14383–14395

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Balaj L, Lessard R, Dai L et al (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180

    PubMed Central  PubMed  Google Scholar 

  49. Choi DS, Lee JM, Park GW et al (2007) Proteomic analysis of microvesicles derived from human colorectal cancer cells. J Proteome Res 6:4646–4655

    CAS  PubMed  Google Scholar 

  50. Gallo A, Tandon M, Alevizos I et al (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7:e30679

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Graner MW, Alzate O, Dechkovskaia AM et al (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23:1541–1557

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Grange C, Tapparo M, Collino F et al (2011) Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res 71:5346–5356

    CAS  PubMed  Google Scholar 

  53. Noerholm M, Balaj L, Limperg T et al (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12:22

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Zhuang G, Wu X, Jiang Z et al (2012) Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J 31:3513–3523

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Baran J, Baj-Krzyworzeka M, Weglarczyk K et al (2010) Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 59:841–850

    CAS  PubMed  Google Scholar 

  56. Marcucci G, Mrozek K, Radmacher MD et al (2009) MicroRNA expression profiling in acute myeloid and chronic lymphocytic leukaemias. Best Pract Res Clin Haematol 22:239–248

    CAS  PubMed  Google Scholar 

  57. Sandvig K, Llorente A (2012) Proteomic analysis of microvesicles released by the human prostate cancer cell line PC-3. Mol Cell Proteomics 11:M111.012914

    PubMed Central  PubMed  Google Scholar 

  58. Zhou Q, Souba WW, Croce CM et al (2010) MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut 59:775–784

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Del Conde I, Bharwani LD, Dietzen DJ et al (2007) Microvesicle-associated tissue factor and Trousseau’s syndrome. J Thromb Haemost 5:70–74

    PubMed Central  PubMed  Google Scholar 

  60. Graves LE, Ariztia EV, Navari JR et al (2004) Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 64:7045–7049

    CAS  PubMed  Google Scholar 

  61. Chen C, Skog J, Hsu CH et al (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10:505–511

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Owen DM, Magenau A, Williamson D et al (2012) The lipid raft hypothesis revisited: new insights on raft composition and function from super-resolution fluorescence microscopy. Bioessays 34:739–747

    CAS  PubMed  Google Scholar 

  63. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    CAS  PubMed  Google Scholar 

  64. Gangalum RK, Atanasov IC, Zhou ZH et al (2011) AlphaB-crystallin is found in detergent-resistant membrane microdomains and is secreted via exosomes from human retinal pigment epithelial cells. J Biol Chem 286:3261–3269

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Lopez JA, del Conde I, Shrimpton CN (2005) Receptors, rafts, and microvesicles in thrombosis and inflammation. J Thromb Haemost 3:1737–1744

    CAS  PubMed  Google Scholar 

  66. Mairhofer M, Steiner M, Mosgoeller W et al (2002) Stomatin is a major lipid-raft component of platelet alpha granules. Blood 100:897–904

    CAS  PubMed  Google Scholar 

  67. Del Conde I, Shrimpton CN, Thiagarajan P et al (2005) Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611

    PubMed  Google Scholar 

  68. Liu ML, Scalia R, Mehta JL et al (2012) Cholesterol-induced membrane microvesicles as novel carriers of damage-associated molecular patterns: mechanisms of formation, action, and detoxification. Arterioscler Thromb Vasc Biol 32:2113–2121

    PubMed  Google Scholar 

  69. Pomorski T, Menon AK (2006) Lipid flippases and their biological functions. Cell Mol Life Sci 63:2908–2921

    CAS  PubMed  Google Scholar 

  70. Seigneuret M, Devaux PF (1984) ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci U S A 81:3751–3755

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Contreras FX, Sanchez-Magraner L, Alonso A et al (2010) Transbilayer (flip-flop) lipid motion and lipid scrambling in membranes. FEBS Lett 584:1779–1786

    CAS  PubMed  Google Scholar 

  72. Dasgupta SK, Abdel-Monem H, Niravath P et al (2009) Lactadherin and clearance of platelet-derived microvesicles. Blood 113:1332–1339

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Lima LG, Chammas R, Monteiro RQ et al (2009) Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett 283:168–175

    CAS  PubMed  Google Scholar 

  74. Collino F, Deregibus MC, Bruno S et al (2010) Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 5:e11803

    PubMed Central  PubMed  Google Scholar 

  75. Meng Y, Kang S, Fishman DA (2005) Lysophosphatidic acid stimulates fas ligand microvesicle release from ovarian cancer cells. Cancer Immunol Immunother 54:807–814

    CAS  PubMed  Google Scholar 

  76. Charras GT, Hu CK, Coughlin M et al (2006) Reassembly of contractile actin cortex in cell blebs. J Cell Biol 175:477–490

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Fackler OT, Grosse R (2008) Cell motility through plasma membrane blebbing. J Cell Biol 181:879–884

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9:690–701

    CAS  PubMed  Google Scholar 

  79. Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7:737–749

    CAS  PubMed  Google Scholar 

  80. Hahmann C, Schroeter T (2010) Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity. Cell Mol Life Sci 67:171–177

    CAS  PubMed  Google Scholar 

  81. Mizuno K (2013) Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation. Cell Signal 25: 457–469

    CAS  PubMed  Google Scholar 

  82. Narumiya S, Ishizaki T, Uehata M (2000) Use and properties of ROCK-specific inhibitor Y-27632. Methods Enzymol 325:273–284

    CAS  PubMed  Google Scholar 

  83. Narumiya S, Tanji M, Ishizaki T (2009) Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev 28:65–76

    CAS  PubMed  Google Scholar 

  84. Sahai E, Ishizaki T, Narumiya S et al (1999) Transformation mediated by RhoA requires activity of ROCK kinases. Curr Biol 9:136–145

    CAS  PubMed  Google Scholar 

  85. Del Vecchio CA, Li G, Wong AJ (2012) Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas. Expert Rev Vaccines 11:133–144

    PubMed  Google Scholar 

  86. Corcoran C, Rani S, O’Brien K et al (2012) Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One 7:e50999

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Lehmann BD, Paine MS, Brooks AM et al (2008) Senescence-associated exosome release from human prostate cancer cells. Cancer Res 68:7864–7871

    CAS  PubMed  Google Scholar 

  88. Shedden K, Xie XT, Chandaroy P et al (2003) Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 63:4331–4337

    CAS  PubMed  Google Scholar 

  89. Svensson KJ, Kucharzewska P, Christianson HC et al (2011) Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc Natl Acad Sci U S A 108:13147–13152

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Erickson JW, Cerione RA (2010) Glutaminase: a hot spot for regulation of cancer cell metabolism? Oncotarget 1:734–740

    PubMed Central  PubMed  Google Scholar 

  91. Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11:325–337

    CAS  PubMed  Google Scholar 

  92. Wilson KF, Erickson JW, Antonyak MA et al (2013) Rho GTPases and their roles in cancer metabolism. Trends Mol Med 19:74–82

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Altieri DC (2008) New wirings in the survivin networks. Oncogene 27:6276–6284

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Cheung CH, Cheng L, Chang KY et al (2011) Investigations of survivin: the past, present and future. Front Biosci 16:952–961

    CAS  Google Scholar 

  95. Honegger A, Leitz J, Bulkescher J et al (2013) Silencing of human papillomavirus (HPV) E6/E7 oncogene expression affects both the contents and amounts of extracellular microvesicles released from HPV-positive cancer cells. Int J Cancer 133:1631–1642. doi:10.1002/ijc.28164

    CAS  PubMed  Google Scholar 

  96. Khan S, Jutzy JM, Aspe JR et al (2011) Survivin is released from cancer cells via exosomes. Apoptosis 16:1–12

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Khan S, Jutzy JM, Valenzuela MM et al (2012) Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS One 7:e46737

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Taylor DD, Gercel-Taylor C, Parker LP (2009) Patient-derived tumor-reactive antibodies as diagnostic markers for ovarian cancer. Gynecol Oncol 115:112–120

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Fujita M, Kinoshita T (2012) GPI-anchor remodeling: potential functions of GPI-anchors in intracellular trafficking and membrane dynamics. Biochim Biophys Acta 1821: 1050–1058

    CAS  PubMed  Google Scholar 

  100. Muller G, Schneider M, Biemer-Daub G et al (2011) Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cell Signal 23: 1207–1223

    PubMed  Google Scholar 

  101. Hao S, Ye Z, Li F et al (2006) Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp Oncol 28:126–131

    CAS  PubMed  Google Scholar 

  102. Hessvik NP, Phuyal S, Brech A et al (2012) Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta 1819:1154–1163

    CAS  PubMed  Google Scholar 

  103. Chiba M, Kimura M, Asari S (2012) Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines. Oncol Rep 28:1551–1558

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Bolukbasi MF, Mizrak A, Ozdener GB et al (2012) miR-1289 and “Zipcode”-like sequence enrich mRNAs in microvesicles. Mol Ther Nucleic Acids 1:e10

    PubMed Central  PubMed  Google Scholar 

  105. Faini M, Beck R, Wieland FT et al (2013) Vesicle coats: structure, function, and general principles of assembly. Trends Cell Biol 23:279–288. doi:10.1016/j.tcb.2013.01.005

    CAS  PubMed  Google Scholar 

  106. Donaldson JG, Jackson CL (2011) ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 12:362–375

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Martins VR, Dias MS, Hainaut P (2013) Tumor-cell-derived microvesicles as carriers of molecular information in cancer. Curr Opin Oncol 25:66–75

    CAS  PubMed  Google Scholar 

  108. Egeblad M, Nakasone ES, Werb Z (2010) Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18: 884–901

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    CAS  PubMed  Google Scholar 

  111. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481:306–313

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Redmond KM, Wilson TR, Johnston PG et al (2008) Resistance mechanisms to cancer chemotherapy. Front Biosci 13:5138–5154

    CAS  PubMed  Google Scholar 

  113. Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26:3291–3310

    CAS  PubMed  Google Scholar 

  114. Campanella C, Bucchieri F, Merendino AM et al (2012) The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities. PLoS One 7:e42008

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Chalmin F, Ladoire S, Mignot G et al (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120:457–471

    CAS  PubMed Central  PubMed  Google Scholar 

  116. McCready J, Sims JD, Chan D et al (2010) Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation. BMC Cancer 10:294

    PubMed Central  PubMed  Google Scholar 

  117. Morimoto RI (2011) The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol 76:91–99

    CAS  PubMed  Google Scholar 

  118. Rappa F, Farina F, Zummo G et al (2012) HSP-molecular chaperones in cancer biogenesis and tumor therapy: an overview. Anticancer Res 32:5139–5150

    CAS  PubMed  Google Scholar 

  119. Safaei R, Larson BJ, Cheng TC et al (2005) Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol Cancer Ther 4:1595–1604

    CAS  PubMed  Google Scholar 

  120. Boing AN, Hau CM, Sturk A et al (2008) Platelet microparticles contain active caspase 3. Platelets 19:96–103

    PubMed  Google Scholar 

  121. Sapet C, Simoncini S, Loriod B et al (2006) Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2. Blood 108:1868–1876

    CAS  PubMed  Google Scholar 

  122. Abid Hussein MN, Boing AN, Sturk A et al (2007) Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb Haemost 98:1096–1107

    PubMed  Google Scholar 

  123. Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3:401–410

    CAS  PubMed  Google Scholar 

  124. Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278:16–27

    CAS  PubMed  Google Scholar 

  125. Dolo V, D’Ascenzo S, Violini S et al (1999) Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis 17:131–140

    CAS  PubMed  Google Scholar 

  126. Janowska-Wieczorek A, Marquez-Curtis LA, Wysoczynski M et al (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46:1199–1209

    PubMed  Google Scholar 

  127. Janowska-Wieczorek A, Wysoczynski M, Kijowski J et al (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113:752–760

    CAS  PubMed  Google Scholar 

  128. Braundmeier AG, Dayger CA, Mehrotra P et al (2012) EMMPRIN is secreted by human uterine epithelial cells in microvesicles and stimulates metalloproteinase production by human uterine fibroblast cells. Reprod Sci 19:1292–1301

    CAS  PubMed  Google Scholar 

  129. Millimaggi D, Mari M, D’Ascenzo S et al (2007) Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 9:349–357

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Abe T, Okamura K, Ono M et al (1993) Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis. J Clin Invest 92:54–61

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Baj-Krzyworzeka M, Szatanek R, Weglarczyk K et al (2006) Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 55:808–818

    CAS  PubMed  Google Scholar 

  132. Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057

    CAS  PubMed  Google Scholar 

  133. Joosse SA, Pantel K (2013) Biologic challenges in the detection of circulating tumor cells. Cancer Res 73:8–11

    CAS  PubMed  Google Scholar 

  134. Peinado H, Aleckovic M, Lavotshkin S et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891

    CAS  PubMed Central  PubMed  Google Scholar 

  135. Shao H, Chung J, Balaj L et al (2012) Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 18:1835–1840

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Aliotta JM, Pereira M, Johnson KW et al (2010) Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp Hematol 38:233–245

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Nilsson J, Skog J, Nordstrand A et al (2009) Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 100:1603–1607

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Cornell University, Ithaca, NY, USA

    Marc A. Antonyak

  2. Department of Molecular Medicine, C3-155 Veterinary Medical Center, Cornell University, Ithaca, NY, 14853-2703, USA

    Richard A. Cerione

Authors
  1. Marc A. Antonyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard A. Cerione
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard A. Cerione .

Editor information

Editors and Affiliations

  1. Universidad Nacional Autónoma de México, Mexico D.F., Mexico

    Martha Robles-Flores

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Antonyak, M.A., Cerione, R.A. (2014). Microvesicles as Mediators of Intercellular Communication in Cancer. In: Robles-Flores, M. (eds) Cancer Cell Signaling. Methods in Molecular Biology, vol 1165. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0856-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0856-1_11

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0855-4

  • Online ISBN: 978-1-4939-0856-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation