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Erschienen in: Cancer Microenvironment 3/2012

01.12.2012 | Original Paper

Exosomes in Cancer Microenvironment and Beyond: have we Overlooked these Extracellular Messengers?

verfasst von: Ruowen Ge, Evan Tan, Soheila Sharghi-Namini, Harry H. Asada

Erschienen in: Cancer Microenvironment | Ausgabe 3/2012

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Abstract

Cancer is a complex organ whose behavior is not only influenced by genetic and epigenetic changes in cancer cells but also by stromal cells, local extracellular matrix and specific tissue architecture. Intercellular communications within the cancer microenvironment are critical to coordinate the assembly of multiple cell types for an amalgamated form and function of a cancer. Exosomes are small membrane vesicles with an endosome origin that are released by cells into the extracellular environment. They carry a cargo of proteins, lipids, and nucleic acids and transfer their cargo to recipient cells and altering the recipient cells’ biochemical composition, signaling pathways, and gene regulation. Exosomes can thus serve as extracellular messengers mediating cell-cell communication. Both cancer cells and stromal cells release exosomes not only into the cancer microenvironment but also into the circulation. In this review, we summarize the research done so far on cancer-derived exosomes and assess their roles as extracellular messengers facilitating cancer progression and metastasis.
Literatur
1.
Zurück zum Zitat Trams EG, Lauter CJ, Salem N, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophy Acta 645(1):63–70CrossRef Trams EG, Lauter CJ, Salem N, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophy Acta 645(1):63–70CrossRef
2.
Zurück zum Zitat Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97(2):329–339PubMedCrossRef Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97(2):329–339PubMedCrossRef
3.
Zurück zum Zitat Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–978PubMedCrossRef Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–978PubMedCrossRef
4.
Zurück zum Zitat Pan BT, Teng K, Wu C, Adam M, Johnstone RM (1985) Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 101(3):942–948PubMedCrossRef Pan BT, Teng K, Wu C, Adam M, Johnstone RM (1985) Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 101(3):942–948PubMedCrossRef
5.
Zurück zum Zitat Johnstone RM, Bianchini A, Teng K (1989) Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. Blood 74(5):1844–1851PubMed Johnstone RM, Bianchini A, Teng K (1989) Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. Blood 74(5):1844–1851PubMed
6.
Zurück zum Zitat Orr L, Adam M, Johnstone RM (1987) Externalization of membrane-bound activities during sheep reticulocyte maturation is temperature and ATP dependent. Biochem Cell Biol 65(12):1080–1090PubMedCrossRef Orr L, Adam M, Johnstone RM (1987) Externalization of membrane-bound activities during sheep reticulocyte maturation is temperature and ATP dependent. Biochem Cell Biol 65(12):1080–1090PubMedCrossRef
7.
Zurück zum Zitat Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3:Unit 3 22 Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3:Unit 3 22
8.
Zurück zum Zitat Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56(2):293–304PubMedCrossRef Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56(2):293–304PubMedCrossRef
9.
Zurück zum Zitat Mathivanan RJSaS (2012) Extracellular microvesicles: the need for internationally recognised nomenclature and stringent purification criteria. J Proteomics Bioinform 5(2):ii Mathivanan RJSaS (2012) Extracellular microvesicles: the need for internationally recognised nomenclature and stringent purification criteria. J Proteomics Bioinform 5(2):ii
10.
Zurück zum Zitat Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113(Pt 19):3365–3374PubMed Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113(Pt 19):3365–3374PubMed
11.
Zurück zum Zitat Bobrie A, Colombo M, Raposo G, Thery C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12(12):1659–1668PubMedCrossRef Bobrie A, Colombo M, Raposo G, Thery C (2011) Exosome secretion: molecular mechanisms and roles in immune responses. Traffic 12(12):1659–1668PubMedCrossRef
12.
Zurück zum Zitat Mathivanan S, Simpson RJ (2009) ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 9(21):4997–5000PubMedCrossRef Mathivanan S, Simpson RJ (2009) ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 9(21):4997–5000PubMedCrossRef
13.
Zurück zum Zitat Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30PubMedCrossRef Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30PubMedCrossRef
15.
Zurück zum Zitat Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 147(3):599–610PubMedCrossRef Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1999) Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 147(3):599–610PubMedCrossRef
16.
Zurück zum Zitat Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23(5):1541–1557PubMedCrossRef Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23(5):1541–1557PubMedCrossRef
17.
Zurück zum Zitat Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65(12):5238–5247PubMedCrossRef Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65(12):5238–5247PubMedCrossRef
18.
Zurück zum Zitat Muntasell A, Berger AC, Roche PA (2007) T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J 26(19):4263–4272PubMedCrossRef Muntasell A, Berger AC, Roche PA (2007) T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J 26(19):4263–4272PubMedCrossRef
19.
Zurück zum Zitat Janiszewski M, Do Carmo AO, Pedro MA, Silva E, Knobel E, Laurindo FRM (2004) Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway. Criti Care Med 32(3):818–825CrossRef Janiszewski M, Do Carmo AO, Pedro MA, Silva E, Knobel E, Laurindo FRM (2004) Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway. Criti Care Med 32(3):818–825CrossRef
20.
Zurück zum Zitat Wolfers J, Lozier A, Raposo G, Regnault A, Théry C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7(3):297–303PubMedCrossRef Wolfers J, Lozier A, Raposo G, Regnault A, Théry C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7(3):297–303PubMedCrossRef
21.
Zurück zum Zitat Lee HM, Choi E-J, Kim JH, Kim TD, Kim Y-K, Kang C, Gho YS (2010) A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells. Biochem Biophy Res Comm 397(2):251–256CrossRef Lee HM, Choi E-J, Kim JH, Kim TD, Kim Y-K, Kang C, Gho YS (2010) A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells. Biochem Biophy Res Comm 397(2):251–256CrossRef
22.
Zurück zum Zitat Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ (2010) Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol 190(6):1079–1091PubMedCrossRef Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ (2010) Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol 190(6):1079–1091PubMedCrossRef
23.
Zurück zum Zitat Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123(Pt 10):1603–1611PubMedCrossRef Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123(Pt 10):1603–1611PubMedCrossRef
24.
Zurück zum Zitat Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G, D’Souza-Schorey C (2009) ARF6–regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885PubMedCrossRef Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G, D’Souza-Schorey C (2009) ARF6–regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885PubMedCrossRef
25.
Zurück zum Zitat Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin. Physiology 20:22–27PubMedCrossRef Hugel B, Martinez MC, Kunzelmann C, Freyssinet JM (2005) Membrane microparticles: two sides of the coin. Physiology 20:22–27PubMedCrossRef
26.
Zurück zum Zitat Lima LG, Chammas R, Monteiro RQ, Moreira ME, Barcinski MA (2009) Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett 283(2):168–175PubMedCrossRef Lima LG, Chammas R, Monteiro RQ, Moreira ME, Barcinski MA (2009) Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett 283(2):168–175PubMedCrossRef
27.
Zurück zum Zitat Morelli AE, Larregina AT, Shufesky WJ, Sullivan MLG, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD, Thomson AW (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104(10):3257–3266PubMedCrossRef Morelli AE, Larregina AT, Shufesky WJ, Sullivan MLG, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD, Thomson AW (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104(10):3257–3266PubMedCrossRef
28.
Zurück zum Zitat Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF, Zhou Q, Sui SF (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11(5):675–687PubMedCrossRef Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF, Zhou Q, Sui SF (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11(5):675–687PubMedCrossRef
29.
Zurück zum Zitat Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, Coscia C, Iessi E, Logozzi M, Molinari A, Colone M, Tatti M, Sargiacomo M, Fais S (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284(49):34211–34222PubMedCrossRef Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, Coscia C, Iessi E, Logozzi M, Molinari A, Colone M, Tatti M, Sargiacomo M, Fais S (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284(49):34211–34222PubMedCrossRef
30.
Zurück zum Zitat Fitzner D, Schnaars M, van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, Regen T, Hanisch UK, Simons M (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 124(Pt 3):447–458PubMedCrossRef Fitzner D, Schnaars M, van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, Regen T, Hanisch UK, Simons M (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 124(Pt 3):447–458PubMedCrossRef
31.
Zurück zum Zitat Segura E, Guerin C, Hogg N, Amigorena S, Thery C (2007) CD8+ dendritic cells use LFA-1 to capture MHC- peptide complexes from exosomes in vivo. J Immunol 179(3):1489–1496PubMed Segura E, Guerin C, Hogg N, Amigorena S, Thery C (2007) CD8+ dendritic cells use LFA-1 to capture MHC- peptide complexes from exosomes in vivo. J Immunol 179(3):1489–1496PubMed
32.
Zurück zum Zitat 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(6):654–659PubMedCrossRef 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(6):654–659PubMedCrossRef
33.
Zurück zum Zitat Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10(5):619–624PubMedCrossRef Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10(5):619–624PubMedCrossRef
34.
Zurück zum Zitat Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476PubMedCrossRef Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476PubMedCrossRef
35.
Zurück zum Zitat Bissell MJ, Hines WC (2011) Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17(3):320–329PubMedCrossRef Bissell MJ, Hines WC (2011) Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17(3):320–329PubMedCrossRef
36.
Zurück zum Zitat Kenny PA, Lee GY, Bissell MJ (2007) Targeting the tumor microenvironment. Front Biosci 12:3468–3474PubMedCrossRef Kenny PA, Lee GY, Bissell MJ (2007) Targeting the tumor microenvironment. Front Biosci 12:3468–3474PubMedCrossRef
37.
Zurück zum Zitat Leibovici J, Itzhaki O, Huszar M, Sinai J (2011) The tumor microenvironment: part 1. Immunotherapy 3(11):1367–1384PubMedCrossRef Leibovici J, Itzhaki O, Huszar M, Sinai J (2011) The tumor microenvironment: part 1. Immunotherapy 3(11):1367–1384PubMedCrossRef
38.
Zurück zum Zitat De Milito A, Marino ML, Fais S (2012) A rationale for the use of proton pump inhibitors as antineoplastic agents. Curr Pharm Des 18(10):1395–1406PubMed De Milito A, Marino ML, Fais S (2012) A rationale for the use of proton pump inhibitors as antineoplastic agents. Curr Pharm Des 18(10):1395–1406PubMed
39.
Zurück zum Zitat Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, De Leon M, Langridge WH, Wall NR (2009) Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. Br J Cancer 100(7):1073–1086PubMedCrossRef Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, De Leon M, Langridge WH, Wall NR (2009) Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. Br J Cancer 100(7):1073–1086PubMedCrossRef
40.
Zurück zum Zitat Keller S, Konig AK, Marme F, Runz S, Wolterink S, Koensgen D, Mustea A, Sehouli J, Altevogt P (2009) Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett 278(1):73–81PubMedCrossRef Keller S, Konig AK, Marme F, Runz S, Wolterink S, Koensgen D, Mustea A, Sehouli J, Altevogt P (2009) Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett 278(1):73–81PubMedCrossRef
41.
Zurück zum Zitat Higginbotham JN, Demory Beckler M, Gephart JD, Franklin JL, Bogatcheva G, Kremers GJ, Piston DW, Ayers GD, McConnell RE, Tyska MJ, Coffey RJ (2011) Amphiregulin exosomes increase cancer cell invasion. Curr Biol 21(9):779–786PubMedCrossRef Higginbotham JN, Demory Beckler M, Gephart JD, Franklin JL, Bogatcheva G, Kremers GJ, Piston DW, Ayers GD, McConnell RE, Tyska MJ, Coffey RJ (2011) Amphiregulin exosomes increase cancer cell invasion. Curr Biol 21(9):779–786PubMedCrossRef
42.
Zurück zum Zitat Deng Z, Cheng Z, Xiang X, Yan J, Zhuang X, Liu C, Jiang H, Ju S, Zhang L, Grizzle W, Mobley J, Roman J, Miller D, Zhang HG (2012) Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression. Am J Pathol 180(1):390–398PubMedCrossRef Deng Z, Cheng Z, Xiang X, Yan J, Zhuang X, Liu C, Jiang H, Ju S, Zhang L, Grizzle W, Mobley J, Roman J, Miller D, Zhang HG (2012) Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression. Am J Pathol 180(1):390–398PubMedCrossRef
43.
Zurück zum Zitat Hood JL, Pan H, Lanza GM, Wickline SA (2009) Paracrine induction of endothelium by tumor exosomes. Lab Invest 89(11):1317–1328PubMedCrossRef Hood JL, Pan H, Lanza GM, Wickline SA (2009) Paracrine induction of endothelium by tumor exosomes. Lab Invest 89(11):1317–1328PubMedCrossRef
44.
Zurück zum Zitat Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, Gho YS (2009) Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556PubMedCrossRef Hong BS, Cho JH, Kim H, Choi EJ, Rho S, Kim J, Kim JH, Choi DS, Kim YK, Hwang D, Gho YS (2009) Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10:556PubMedCrossRef
45.
Zurück zum Zitat Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A 106(10):3794–3799PubMedCrossRef Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A 106(10):3794–3799PubMedCrossRef
46.
Zurück zum Zitat Gesierich S, Berezovskiy I, Ryschich E, Zoller M (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res 66(14):7083–7094PubMedCrossRef Gesierich S, Berezovskiy I, Ryschich E, Zoller M (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res 66(14):7083–7094PubMedCrossRef
47.
Zurück zum Zitat Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, Lochnit G, Preissner KT, Zoller M (2010) Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 70(4):1668–1678PubMedCrossRef Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, Lochnit G, Preissner KT, Zoller M (2010) Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 70(4):1668–1678PubMedCrossRef
48.
Zurück zum Zitat Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9(6):1085–1099PubMedCrossRef Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9(6):1085–1099PubMedCrossRef
49.
Zurück zum Zitat Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, Leek R, Edelmann M, Kessler B, Sainson RC, Sargent I, Li JL, Harris AL (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116(13):2385–2394PubMedCrossRef Sheldon H, Heikamp E, Turley H, Dragovic R, Thomas P, Oon CE, Leek R, Edelmann M, Kessler B, Sainson RC, Sargent I, Li JL, Harris AL (2010) New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116(13):2385–2394PubMedCrossRef
50.
Zurück zum Zitat Webber J, Steadman R, Mason MD, Tabi Z, Clayton A (2010) Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 70(23):9621–9630PubMedCrossRef Webber J, Steadman R, Mason MD, Tabi Z, Clayton A (2010) Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 70(23):9621–9630PubMedCrossRef
51.
Zurück zum Zitat Runz S, Keller S, Rupp C, Stoeck A, Issa Y, Koensgen D, Mustea A, Sehouli J, Kristiansen G, Altevogt P (2007) Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol 107(3):563–571PubMedCrossRef Runz S, Keller S, Rupp C, Stoeck A, Issa Y, Koensgen D, Mustea A, Sehouli J, Kristiansen G, Altevogt P (2007) Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol 107(3):563–571PubMedCrossRef
52.
Zurück zum Zitat Dolo V, D’Ascenzo S, Violini S, Pompucci L, Festuccia C, Ginestra A, Vittorelli ML, Canevari S, Pavan A (1999) Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis 17(2):131–140PubMedCrossRef Dolo V, D’Ascenzo S, Violini S, Pompucci L, Festuccia C, Ginestra A, Vittorelli ML, Canevari S, Pavan A (1999) Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis 17(2):131–140PubMedCrossRef
53.
Zurück zum Zitat Dolo V, Ginestra A, Cassara D, Ghersi G, Nagase H, Vittorelli ML (1999) Shed membrane vesicles and selective localization of gelatinases and MMP-9/TIMP-1 complexes. Ann NY Acad Sci 878:497–499PubMedCrossRef Dolo V, Ginestra A, Cassara D, Ghersi G, Nagase H, Vittorelli ML (1999) Shed membrane vesicles and selective localization of gelatinases and MMP-9/TIMP-1 complexes. Ann NY Acad Sci 878:497–499PubMedCrossRef
54.
Zurück zum Zitat Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA (2004) Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 64(19):7045–7049PubMedCrossRef Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA (2004) Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 64(19):7045–7049PubMedCrossRef
55.
Zurück zum Zitat Gutwein P, Stoeck A, Riedle S, Gast D, Runz S, Condon TP, Marme A, Phong MC, Linderkamp O, Skorokhod A, Altevogt P (2005) Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin Cancer Res 11(7):2492–2501PubMedCrossRef Gutwein P, Stoeck A, Riedle S, Gast D, Runz S, Condon TP, Marme A, Phong MC, Linderkamp O, Skorokhod A, Altevogt P (2005) Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin Cancer Res 11(7):2492–2501PubMedCrossRef
56.
Zurück zum Zitat Stoeck A, Keller S, Riedle S, Sanderson MP, Runz S, Le Naour F, Gutwein P, Ludwig A, Rubinstein E, Altevogt P (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393(Pt 3):609–618PubMed Stoeck A, Keller S, Riedle S, Sanderson MP, Runz S, Le Naour F, Gutwein P, Ludwig A, Rubinstein E, Altevogt P (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393(Pt 3):609–618PubMed
57.
Zurück zum Zitat Jung T, Castellana D, Klingbeil P, Cuesta Hernandez I, Vitacolonna M, Orlicky DJ, Roffler SR, Brodt P, Zoller M (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11(10):1093–1105PubMed Jung T, Castellana D, Klingbeil P, Cuesta Hernandez I, Vitacolonna M, Orlicky DJ, Roffler SR, Brodt P, Zoller M (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11(10):1093–1105PubMed
58.
Zurück zum Zitat Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78(9):838–848PubMedCrossRef Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78(9):838–848PubMedCrossRef
59.
Zurück zum Zitat Zamarron BF, Chen W (2011) Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci 7(5):651–658PubMedCrossRef Zamarron BF, Chen W (2011) Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci 7(5):651–658PubMedCrossRef
60.
Zurück zum Zitat Kees T, Egeblad M (2011) Innate immune cells in breast cancer—from villains to heroes? J Mammary Gland Biol Neoplasia 16(3):189–203PubMedCrossRef Kees T, Egeblad M (2011) Innate immune cells in breast cancer—from villains to heroes? J Mammary Gland Biol Neoplasia 16(3):189–203PubMedCrossRef
61.
Zurück zum Zitat Bremnes RM, Al-Shibli K, Donnem T, Sirera R, Al-Saad S, Andersen S, Stenvold H, Camps C, Busund LT (2011) The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on non-small cell lung cancer. J Thorac Oncol 6(4):824–833PubMedCrossRef Bremnes RM, Al-Shibli K, Donnem T, Sirera R, Al-Saad S, Andersen S, Stenvold H, Camps C, Busund LT (2011) The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on non-small cell lung cancer. J Thorac Oncol 6(4):824–833PubMedCrossRef
62.
Zurück zum Zitat Viaud S, Thery C, Ploix S, Tursz T, Lapierre V, Lantz O, Zitvogel L, Chaput N (2010) Dendritic cell-derived exosomes for cancer immunotherapy: what’s next? Cancer Res 70(4):1281–1285PubMedCrossRef Viaud S, Thery C, Ploix S, Tursz T, Lapierre V, Lantz O, Zitvogel L, Chaput N (2010) Dendritic cell-derived exosomes for cancer immunotherapy: what’s next? Cancer Res 70(4):1281–1285PubMedCrossRef
63.
Zurück zum Zitat Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113(5):752–760PubMedCrossRef Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113(5):752–760PubMedCrossRef
64.
Zurück zum Zitat Janowska-Wieczorek A, Marquez-Curtis LA, Wysoczynski M, Ratajczak MZ (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46(7):1199–1209PubMedCrossRef Janowska-Wieczorek A, Marquez-Curtis LA, Wysoczynski M, Ratajczak MZ (2006) Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46(7):1199–1209PubMedCrossRef
65.
Zurück zum Zitat Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110(7):2440–2448PubMedCrossRef Deregibus MC, Cantaluppi V, Calogero R, Lo Iacono M, Tetta C, Biancone L, Bruno S, Bussolati B, Camussi G (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110(7):2440–2448PubMedCrossRef
66.
Zurück zum Zitat Campello E, Spiezia L, Radu CM, Bulato C, Castelli M, Gavasso S, Simioni P (2011) Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism. Thromb Res 127(5):473–477PubMedCrossRef Campello E, Spiezia L, Radu CM, Bulato C, Castelli M, Gavasso S, Simioni P (2011) Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism. Thromb Res 127(5):473–477PubMedCrossRef
67.
Zurück zum Zitat Admyre C, Telemo E, Almqvist N, Lötvall J, Lahesmaa R, Scheynius A, Gabrielsson S (2008) Exosomes—nanovesicles with possible roles in allergic inflammation. Allergy 63(4):404–408PubMedCrossRef Admyre C, Telemo E, Almqvist N, Lötvall J, Lahesmaa R, Scheynius A, Gabrielsson S (2008) Exosomes—nanovesicles with possible roles in allergic inflammation. Allergy 63(4):404–408PubMedCrossRef
68.
Zurück zum Zitat Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD (2007) MHC class II + exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J Immuno 179(4):2235–2241 Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD (2007) MHC class II + exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J Immuno 179(4):2235–2241
69.
Zurück zum Zitat Taylor DD, Gercel-Taylor C (2011) Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33(5):441–454PubMedCrossRef Taylor DD, Gercel-Taylor C (2011) Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33(5):441–454PubMedCrossRef
71.
Zurück zum Zitat Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S, Rivoltini L (2008) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15(1):80–88PubMedCrossRef Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S, Rivoltini L (2008) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15(1):80–88PubMedCrossRef
72.
Zurück zum Zitat Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z (2008) Human tumor-derived exosomes down- modulate NKG2D expression. J Immuno 180(11):7249–7258 Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z (2008) Human tumor-derived exosomes down- modulate NKG2D expression. J Immuno 180(11):7249–7258
73.
Zurück zum Zitat Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z (2007) Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res 67(15):7458–7466PubMedCrossRef Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z (2007) Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res 67(15):7458–7466PubMedCrossRef
74.
Zurück zum Zitat Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL (2009) Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immuno 183(6):3720–3730CrossRef Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL (2009) Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immuno 183(6):3720–3730CrossRef
75.
Zurück zum Zitat Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL (2010) Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One 5(7):e11469–e11469PubMedCrossRef Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL (2010) Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One 5(7):e11469–e11469PubMedCrossRef
76.
Zurück zum Zitat Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immuno 9(3):162–174CrossRef Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immuno 9(3):162–174CrossRef
77.
Zurück zum Zitat Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, Grizzle WE, Mobley J, Zhang HG (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124(11):2621–2633PubMedCrossRef Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, Grizzle WE, Mobley J, Zhang HG (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124(11):2621–2633PubMedCrossRef
78.
Zurück zum Zitat Yang C, Kim S-H, Bianco NR, Robbins PD (2011) Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model. PLoS One 6(8):e22517–e22517PubMedCrossRef Yang C, Kim S-H, Bianco NR, Robbins PD (2011) Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model. PLoS One 6(8):e22517–e22517PubMedCrossRef
79.
Zurück zum Zitat Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, Zeidler R (2011) Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immuno Immunothe: CII 60(5):639–648CrossRef Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, Zeidler R (2011) Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immuno Immunothe: CII 60(5):639–648CrossRef
80.
Zurück zum Zitat Pant S, Hilton H, Burczynski ME (2011) The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacology Pant S, Hilton H, Burczynski ME (2011) The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacology
81.
Zurück zum Zitat Taylor DD, Homesley HD, Doellgast GJ (1980) Binding of specific peroxidase-labeled antibody to placental- type phosphatase on tumor-derived membrane fragments. Cancer Res 40(11):4064–4069PubMed Taylor DD, Homesley HD, Doellgast GJ (1980) Binding of specific peroxidase-labeled antibody to placental- type phosphatase on tumor-derived membrane fragments. Cancer Res 40(11):4064–4069PubMed
82.
Zurück zum Zitat Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110(1):13–21PubMedCrossRef Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110(1):13–21PubMedCrossRef
83.
Zurück zum Zitat Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH (2009) Exosomal microRNA: a diagnostic marker for lung cancer. Clinical lung cancer 10(1):42–46PubMedCrossRef Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH (2009) Exosomal microRNA: a diagnostic marker for lung cancer. Clinical lung cancer 10(1):42–46PubMedCrossRef
84.
Zurück zum Zitat Welton JL, Khanna S, Giles PJ, Brennan P, Brewis IA, Staffurth J, Mason MD, Clayton A (2010) Proteomics analysis of bladder cancer exosomes. Mol Cell Proteomics: MCP 9(6):1324–1338PubMedCrossRef Welton JL, Khanna S, Giles PJ, Brennan P, Brewis IA, Staffurth J, Mason MD, Clayton A (2010) Proteomics analysis of bladder cancer exosomes. Mol Cell Proteomics: MCP 9(6):1324–1338PubMedCrossRef
85.
Zurück zum Zitat Nilsson J, Skog J, Nordstrand A, Baranov V, Mincheva-Nilsson L, Breakefield XO, Widmark A (2009) Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 100(10):1603–1607PubMedCrossRef Nilsson J, Skog J, Nordstrand A, Baranov V, Mincheva-Nilsson L, Breakefield XO, Widmark A (2009) Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 100(10):1603–1607PubMedCrossRef
Metadaten
Titel
Exosomes in Cancer Microenvironment and Beyond: have we Overlooked these Extracellular Messengers?
verfasst von
Ruowen Ge
Evan Tan
Soheila Sharghi-Namini
Harry H. Asada
Publikationsdatum
01.12.2012
Verlag
Springer Netherlands
Erschienen in
Cancer Microenvironment / Ausgabe 3/2012
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-012-0110-2

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