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Extracellular Vesicles in the Tumor Microenvironment: Various Implications in Tumor Progression

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1259))

Abstract

Extracellular vesicle (EV) shedding is a biologically conserved cellular process across virtually every cell type. In cancer, EVs shed from tumor and stromal cells to the tumor microenvironment play a major role in determining tumor fate, which to a large extent is dictated by the biologically active cargo contained in EVs. Current understanding of various cancer-associated EVs has enabled the outlining of mechanistic connections between cargo and tumor-promoting functions. In this chapter, we describe examples of EV-mediated communication between tumor cells and stromal cells, highlighting the molecular constituents responsible for pro-tumorigenic effects. Furthermore, we discuss the roles of matrix-degrading EVs in cell invasion. Finally, we summarize research on the potential use of EVs as a novel approach to cancer therapeutics.

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References

  1. 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):619–624. https://doi.org/10.1038/ncb1725

    Article  CAS  PubMed  Google Scholar 

  2. 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):3794–3799. https://doi.org/10.1073/pnas.0804543106

    Article  PubMed  PubMed Central  Google Scholar 

  3. Anderson HC (1969) Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol 41(1):59–72. https://doi.org/10.1083/jcb.41.1.59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Andreola G, Rivoltini L, Castelli C, Huber V, Perego P, Deho P, Squarcina P, Accornero P, Lozupone F, Lugini L, Stringaro A, Molinari A, Arancia G, Gentile M, Parmiani G, Fais S (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195(10):1303–1316. https://doi.org/10.1084/jem.20011624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Benz EW Jr, Moses HL (1974) Small, virus-like particles detected in bovine sera by electron microscopy. J Natl Cancer Inst 52(6):1931–1934. https://doi.org/10.1093/jnci/52.6.1931

    Article  PubMed  Google Scholar 

  6. Bielenberg DR, Zetter BR (2015) The contribution of angiogenesis to the process of metastasis. Cancer J 21(4):267–273. https://doi.org/10.1097/PPO.0000000000000138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bonnans C, Chou J, Werb Z (2014) Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 15(12):786–801. https://doi.org/10.1038/nrm3904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Carter DRF, Clayton A, Devitt A, Hunt S, Lambert DW (2018) Extracellular vesicles in the tumour microenvironment. Philos Trans R Soc Lond Ser B Biol Sci 373(1737):20160475. https://doi.org/10.1098/rstb.2016.0475

    Article  Google Scholar 

  9. Chargaff E, West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166(1):189–197

    CAS  PubMed  Google Scholar 

  10. Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, Xia H, Man Q, Zhong W, Antelo LF, Wu B, Xiong X, Liu X, Guan L, Li T, Liu S, Yang R, Lu Y, Dong L, McGettigan S, Somasundaram R, Radhakrishnan R, Mills G, Lu Y, Kim J, Chen YH, Dong H, Zhao Y, Karakousis GC, Mitchell TC, Schuchter LM, Herlyn M, Wherry EJ, Xu X, Guo W (2018) Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 560(7718):382–386. https://doi.org/10.1038/s41586-018-0392-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y, Tu Q, Yin D, Lin D, Wong PP, Huang D, Xing Y, Zhao J, Li M, Liu Q, Su F, Su S, Song E (2019) Extracellular vesicle-packaged HIF-1alpha-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol 21(4):498–510. https://doi.org/10.1038/s41556-019-0299-0

    Article  CAS  PubMed  Google Scholar 

  12. Chulpanova DS, Kitaeva KV, James V, Rizvanov AA, Solovyeva VV (2018) Therapeutic prospects of extracellular vesicles in cancer treatment. Front Immunol 9:1534. https://doi.org/10.3389/fimmu.2018.01534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Clancy JW, Tricarico CJ, D’Souza-Schorey C (2015) Tumor-derived microvesicles in the tumor microenvironment: how vesicle heterogeneity can shape the future of a rapidly expanding field. BioEssays 37(12):1309–1316. https://doi.org/10.1002/bies.201500068

    Article  CAS  PubMed  Google Scholar 

  14. Clancy JW, Tricarico CJ, Marous DR, D’Souza-Schorey C (2019) Coordinated regulation of intracellular fascin distribution governs tumor microvesicle release and invasive cell capacity. Mol Cell Biol 39(3). https://doi.org/10.1128/MCB.00264-18

  15. Cukierman E, Pankov R, Yamada KM (2002) Cell interactions with three-dimensional matrices. Curr Opin Cell Biol 14(5):633–639

    Article  CAS  PubMed  Google Scholar 

  16. Dorsam B, Reiners KS, von Strandmann EP (2018) Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance. Philos Trans R Soc Lond Ser B Biol Sci 373(1737):20160481. https://doi.org/10.1098/rstb.2016.0481

    Article  CAS  Google Scholar 

  17. Dourado MR, Korvala J, Astrom P, De Oliveira CE, Cervigne NK, Mofatto LS, Campanella Bastos D, Pereira Messetti AC, Graner E, Paes Leme AF, Coletta RD, Salo T (2019) Extracellular vesicles derived from cancer-associated fibroblasts induce the migration and invasion of oral squamous cell carcinoma. J Extracell Vesicles 8(1):1578525. https://doi.org/10.1080/20013078.2019.1578525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fackler OT, Grosse R (2008) Cell motility through plasma membrane blebbing. J Cell Biol 181(6):879–884. https://doi.org/10.1083/jcb.200802081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Feng Q, Zhang C, Lum D, Druso JE, Blank B, Wilson KF, Welm A, Antonyak MA, Cerione RA (2017) A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis. Nat Commun 8:14450. https://doi.org/10.1038/ncomms14450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gilles C, Newgreen DF, Sato H, Thompson EW (2005) Matrix metalloproteases and epithelial-to-mesenchymal transition: implications for carcinoma metastasis. In: Rise and fall of epithelial phenotype: concepts of epithelial-mesenchymal transition. Landes Bioscience/Eurekah.com; Kluwer Academic/Plenum Publishers, Georgetown, Tex., U.S.A, New York, N.Y., U.S.A., 323 pages

    Google Scholar 

  21. Guan XW, Zhao F, Wang JY, Wang HY, Ge SH, Wang X, Zhang L, Liu R, Ba Y, Li HL, Deng T, Zhou LK, Bai M, Ning T, Zhang HY, Huang DZ (2017) Tumor microenvironment interruption: a novel anti-cancer mechanism of Proton-pump inhibitor in gastric cancer by suppressing the release of microRNA-carrying exosomes. Am J Cancer Res 7(9):1913–1925

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Guo S, Deng CX (2018) Effect of stromal cells in tumor microenvironment on metastasis initiation. Int J Biol Sci 14(14):2083–2093. https://doi.org/10.7150/ijbs.25720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Halachmi E, Witz IP (1989) Differential tumorigenicity of 3T3 cells transformed in vitro with polyoma virus and in vivo selection for high tumorigenicity. Cancer Res 49(9):2383–2389

    CAS  PubMed  Google Scholar 

  24. Han L, Lam EW, Sun Y (2019) Extracellular vesicles in the tumor microenvironment: old stories, but new tales. Mol Cancer 18(1):59. https://doi.org/10.1186/s12943-019-0980-8

    Article  PubMed  PubMed Central  Google Scholar 

  25. Hargett LA, Bauer NN (2013) On the origin of microparticles: from “platelet dust” to mediators of intercellular communication. Pulm Circ 3(2):329–340. https://doi.org/10.4103/2045-8932.114760

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hoshino D, Kirkbride KC, Costello K, Clark ES, Sinha S, Grega-Larson N, Tyska MJ, Weaver AM (2013) Exosome secretion is enhanced by invadopodia and drives invasive behavior. Cell Rep 5(5):1159–1168. https://doi.org/10.1016/j.celrep.2013.10.050

    Article  CAS  PubMed  Google Scholar 

  27. Im EJ, Lee CH, Moon PG, Rangaswamy GG, Lee B, Lee JM, Lee JC, Jee JG, Bae JS, Kwon TK, Kang KW, Jeong MS, Lee JE, Jung HS, Ro HJ, Jun S, Kang W, Seo SY, Cho YE, Song BJ, Baek MC (2019) Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A. Nat Commun 10(1):1387. https://doi.org/10.1038/s41467-019-09387-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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):752–760. https://doi.org/10.1002/ijc.20657

    Article  CAS  PubMed  Google Scholar 

  29. Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M (2014) A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta 1846(1):75–87. https://doi.org/10.1016/j.bbcan.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  30. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262(19):9412–9420

    CAS  PubMed  Google Scholar 

  31. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6(5):392–401. https://doi.org/10.1038/nrc1877

    Article  CAS  PubMed  Google Scholar 

  32. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL (2005) Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res 11(3):1010–1020

    CAS  PubMed  Google Scholar 

  33. Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, Inal JM, Bell JD, Lange S (2018) Cannabidiol (CBD) is a novel inhibitor for exosome and microvesicle (EMV) release in cancer. Front Pharmacol 9:889. https://doi.org/10.3389/fphar.2018.00889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM (2015) Cancer invasion: patterns and mechanisms. Acta Nat 7(2):17–28

    Article  CAS  Google Scholar 

  35. Kuchuk O, Tuccitto A, Citterio D, Huber V, Camisaschi C, Milione M, Vergani B, Villa A, Alison MR, Carradori S, Supuran CT, Rivoltini L, Castelli C, Mazzaferro V (2018) pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma. Onco Targets Ther 7(7):e1445452. https://doi.org/10.1080/2162402X.2018.1445452

    Article  Google Scholar 

  36. Lane RE, Korbie D, Hill MM, Trau M (2018) Extracellular vesicles as circulating cancer biomarkers: opportunities and challenges. Clin Transl Med 7(1):14. https://doi.org/10.1186/s40169-018-0192-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Langley RR, Fidler IJ (2011) The seed and soil hypothesis revisited – the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128(11):2527–2535. https://doi.org/10.1002/ijc.26031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Leca J, Martinez S, Lac S, Nigri J, Secq V, Rubis M, Bressy C, Serge A, Lavaut MN, Dusetti N, Loncle C, Roques J, Pietrasz D, Bousquet C, Garcia S, Granjeaud S, Ouaissi M, Bachet JB, Brun C, Iovanna JL, Zimmermann P, Vasseur S, Tomasini R (2016) Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J Clin Invest 126(11):4140–4156. https://doi.org/10.1172/JCI87734

    Article  PubMed  PubMed Central  Google Scholar 

  39. Li P, Feng J, Liu Y, Liu Q, Fan L, Liu Q, She X, Liu C, Liu T, Zhao C, Wang W, Li G, Wu M (2017) Novel therapy for glioblastoma multiforme by restoring LRRC4 in tumor cells: LRRC4 inhibits tumor-infiltrating regulatory T cells by cytokine and programmed cell death 1-containing exosomes. Front Immunol 8:1748. https://doi.org/10.3389/fimmu.2017.01748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang HG (2006) Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 176(3):1375–1385. https://doi.org/10.4049/jimmunol.176.3.1375

    Article  CAS  PubMed  Google Scholar 

  41. Lombardo G, Dentelli P, Togliatto G, Rosso A, Gili M, Gallo S, Deregibus MC, Camussi G, Brizzi MF (2016) Activated Stat5 trafficking via endothelial cell-derived extracellular vesicles controls IL-3 pro-angiogenic paracrine action. Sci Rep 6:25689. https://doi.org/10.1038/srep25689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, Buchanan M, Hosein AN, Basik M, Wrana JL (2012) Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151(7):1542–1556. https://doi.org/10.1016/j.cell.2012.11.024

    Article  CAS  PubMed  Google Scholar 

  43. Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S, Grivel JC (2019) Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance. Mol Cancer 18(1):55. https://doi.org/10.1186/s12943-019-0965-7

    Article  PubMed  PubMed Central  Google Scholar 

  44. Massi P, Solinas M, Cinquina V, Parolaro D (2013) Cannabidiol as potential anticancer drug. Br J Clin Pharmacol 75(2):303–312. https://doi.org/10.1111/j.1365-2125.2012.04298.x

    Article  CAS  PubMed  Google Scholar 

  45. 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):1875–1885. https://doi.org/10.1016/j.cub.2009.09.059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Naito Y, Yoshioka Y, Yamamoto Y, Ochiya T (2017) How cancer cells dictate their microenvironment: present roles of extracellular vesicles. Cell Mol Life Sci 74(4):697–713. https://doi.org/10.1007/s00018-016-2346-3

    Article  CAS  PubMed  Google Scholar 

  47. Naito Y, Yamamoto Y, Sakamoto N, Shimomura I, Kogure A, Kumazaki M, Yokoi A, Yashiro M, Kiyono T, Yanagihara K, Takahashi RU, Hirakawa K, Yasui W, Ochiya T (2019) Cancer extracellular vesicles contribute to stromal heterogeneity by inducing chemokines in cancer-associated fibroblasts. Oncogene 38(28):5566–5579. https://doi.org/10.1038/s41388-019-0832-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nawaz M, Shah N, Zanetti BR, Maugeri M, Silvestre RN, Fatima F, Neder L, Valadi H (2018) Extracellular vesicles and matrix remodeling enzymes: the emerging roles in extracellular matrix remodeling, progression of diseases and tissue repair. Cell 7(10). https://doi.org/10.3390/cells7100167

  49. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M (2006) Angiogenesis in cancer. Vasc Health Risk Manag 2(3):213–219. https://doi.org/10.2147/vhrm.2006.2.3.213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 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):34211–34222. https://doi.org/10.1074/jbc.M109.041152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pathria P, Louis TL, Varner JA (2019) Targeting tumor-associated macrophages in cancer. Trends Immunol 40(4):310–327. https://doi.org/10.1016/j.it.2019.02.003

    Article  CAS  PubMed  Google Scholar 

  52. Poincloux R, Lizarraga F, Chavrier P (2009) Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci 122(Pt 17):3015–3024. https://doi.org/10.1242/jcs.034561

    Article  CAS  PubMed  Google Scholar 

  53. Poste G, Nicolson GL (1980) Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. Proc Natl Acad Sci U S A 77(1):399–403. https://doi.org/10.1073/pnas.77.1.399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Qin X, Yu S, Zhou L, Shi M, Hu Y, Xu X, Shen B, Liu S, Yan D, Feng J (2017) Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner. Int J Nanomedicine 12:3721–3733. https://doi.org/10.2147/IJN.S131516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rabe DC, Rustandy FD, Lee J, Rosner MR (2018) Tumor extracellular vesicles are required for tumor-associated macrophage. status (unpublished; manuscript in preparation)

    Google Scholar 

  56. Rayamajhi S, Nguyen TDT, Marasini R, Aryal S (2019) Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery. Acta Biomater 94:482–494. https://doi.org/10.1016/j.actbio.2019.05.054

    Article  CAS  PubMed  Google Scholar 

  57. Ren J, Ding L, Zhang D, Shi G, Xu Q, Shen S, Wang Y, Wang T, Hou Y (2018) Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19. Theranostics 8(14):3932–3948. https://doi.org/10.7150/thno.25541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Revach OY, Geiger B (2014) The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion. Cell Adhes Migr 8(3):215–225. https://doi.org/10.4161/cam.27842

    Article  Google Scholar 

  59. Rivoltini L, Chiodoni C, Squarcina P, Tortoreto M, Villa A, Vergani B, Burdek M, Botti L, Arioli I, Cova A, Mauri G, Vergani E, Bianchi B, Della Mina P, Cantone L, Bollati V, Zaffaroni N, Gianni AM, Colombo MP, Huber V (2016) TNF-related apoptosis-inducing ligand (TRAIL)-armed exosomes deliver proapoptotic signals to tumor site. Clin Cancer Res 22(14):3499–3512. https://doi.org/10.1158/1078-0432.CCR-15-2170

    Article  CAS  PubMed  Google Scholar 

  60. Rong L, Li R, Li S, Luo R (2016) Immunosuppression of breast cancer cells mediated by transforming growth factor-beta in exosomes from cancer cells. Oncol Lett 11(1):500–504. https://doi.org/10.3892/ol.2015.3841

    Article  CAS  PubMed  Google Scholar 

  61. Saari H, Lazaro-Ibanez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M (2015) Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Release 220(Pt B):727–737. https://doi.org/10.1016/j.jconrel.2015.09.031

    Article  CAS  PubMed  Google Scholar 

  62. Sahai E, Marshall CJ (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol 5(8):711–719. https://doi.org/10.1038/ncb1019

    Article  CAS  PubMed  Google Scholar 

  63. Sakurai-Yageta M, Recchi C, Le Dez G, Sibarita JB, Daviet L, Camonis J, D’Souza-Schorey C, Chavrier P (2008) The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA. J Cell Biol 181(6):985–998. https://doi.org/10.1083/jcb.200709076

    Article  PubMed  PubMed Central  Google Scholar 

  64. Sedgwick AE, Clancy JW, Olivia Balmert M, D’Souza-Schorey C (2015) Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci Rep 5:14748. https://doi.org/10.1038/srep14748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H (2015) Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel) 7(4):2443–2458. https://doi.org/10.3390/cancers7040902

    Article  Google Scholar 

  66. Shinohara H, Kuranaga Y, Kumazaki M, Sugito N, Yoshikawa Y, Takai T, Taniguchi K, Ito Y, Akao Y (2017) Regulated polarization of tumor-associated macrophages by miR-145 via colorectal cancer-derived extracellular vesicles. J Immunol 199(4):1505–1515. https://doi.org/10.4049/jimmunol.1700167

    Article  CAS  PubMed  Google Scholar 

  67. Skalnikova HK, Bohuslavova B, Turnovcova K, Juhasova J, Juhas S, Rodinova M, Vodicka P (2019) Isolation and characterization of small extracellular vesicles from porcine blood plasma, cerebrospinal fluid, and seminal plasma. Proteomes 7(2). https://doi.org/10.3390/proteomes7020017

  68. Sruthi TV, Edatt L, Raji GR, Kunhiraman H, Shankar SS, Shankar V, Ramachandran V, Poyyakkara A, Kumar SVB (2018) Horizontal transfer of miR-23a from hypoxic tumor cell colonies can induce angiogenesis. J Cell Physiol 233(4):3498–3514. https://doi.org/10.1002/jcp.26202

    Article  CAS  PubMed  Google Scholar 

  69. Steffen A, Le Dez G, Poincloux R, Recchi C, Nassoy P, Rottner K, Galli T, Chavrier P (2008) MT1-MMP-dependent invasion is regulated by TI-VAMP/VAMP7. Curr Biol 18(12):926–931. https://doi.org/10.1016/j.cub.2008.05.044

    Article  CAS  PubMed  Google Scholar 

  70. Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM (2015) Directional cell movement through tissues is controlled by exosome secretion. Nat Commun 6:7164. https://doi.org/10.1038/ncomms8164

    Article  CAS  PubMed  Google Scholar 

  71. Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL, Boyiadzis M (2011) Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica 96(9):1302–1309. https://doi.org/10.3324/haematol.2010.039743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Tang K, Zhang Y, Zhang H, Xu P, Liu J, Ma J, Lv M, Li D, Katirai F, Shen GX, Zhang G, Feng ZH, Ye D, Huang B (2012) Delivery of chemotherapeutic drugs in tumour cell-derived microparticles. Nat Commun 3:1282. https://doi.org/10.1038/ncomms2282

    Article  CAS  PubMed  Google Scholar 

  73. 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):4064–4069

    CAS  PubMed  Google Scholar 

  74. Toffoli G, Hadla M, Corona G, Caligiuri I, Palazzolo S, Semeraro S, Gamini A, Canzonieri V, Rizzolio F (2015) Exosomal doxorubicin reduces the cardiac toxicity of doxorubicin. Nanomedicine (Lond) 10(19):2963–2971. https://doi.org/10.2217/nnm.15.118

    Article  CAS  Google Scholar 

  75. Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara H, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Choi BK, Kwon BS (2015) Immune evasion in cancer: mechanistic basis and therapeutic strategies. Semin Cancer Biol 35 Suppl:S185–S198. https://doi.org/10.1016/j.semcancer.2015.03.004

    Article  CAS  PubMed  Google Scholar 

  76. Vizovisek M, Fonovic M, Turk B (2019) Cysteine cathepsins in extracellular matrix remodeling: extracellular matrix degradation and beyond. Matrix Biol 75–76:141–159. https://doi.org/10.1016/j.matbio.2018.01.024

    Article  CAS  PubMed  Google Scholar 

  77. Vu LT, Peng B, Zhang DX, Ma V, Mathey-Andrews CA, Lam CK, Kiomourtzis T, Jin J, McReynolds L, Huang L, Grimson A, Cho WC, Lieberman J, Le MT (2019) Tumor-secreted extracellular vesicles promote the activation of cancer-associated fibroblasts via the transfer of microRNA-125b. J Extracell Vesicles 8(1):1599680. https://doi.org/10.1080/20013078.2019.1599680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10(1):45–65. https://doi.org/10.1038/sj.cdd.4401189

    Article  CAS  PubMed  Google Scholar 

  79. Walczak H (2013) Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb Perspect Biol 5(5):a008698. https://doi.org/10.1101/cshperspect.a008698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, Gong Z, Zhang S, Zhou J, Cao K, Li X, Xiong W, Li G, Zeng Z, Guo C (2017) Role of tumor microenvironment in tumorigenesis. J Cancer 8(5):761–773. https://doi.org/10.7150/jca.17648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Weaver BA (2014) How Taxol/paclitaxel kills cancer cells. Mol Biol Cell 25(18):2677–2681. https://doi.org/10.1091/mbc.E14-04-0916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13(3):269–288. https://doi.org/10.1111/j.1365-2141.1967.tb08741.x

    Article  CAS  PubMed  Google Scholar 

  83. Wu B, Liu J, Zhao R, Li Y, Peer J, Braun AL, Zhao L, Wang Y, Tong Z, Huang Y, Zheng JC (2018) Glutaminase 1 regulates the release of extracellular vesicles during neuroinflammation through key metabolic intermediate alpha-ketoglutarate. J Neuroinflammation 15(1):79. https://doi.org/10.1186/s12974-018-1120-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Wynn TA, Chawla A, Pollard JW (2013) Macrophage biology in development, homeostasis and disease. Nature 496(7446):445–455. https://doi.org/10.1038/nature12034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Kramer-Albers EM, Laitinen S, Lasser C, Lener T, Ligeti E, Line A, Lipps G, Llorente A, Lotvall J, Mancek-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-’t Hoen EN, Nyman TA, O’Driscoll L, Olivan M, Oliveira C, Pallinger E, Del Portillo HA, Reventos J, Rigau M, Rohde E, Sammar M, Sanchez-Madrid F, Santarem N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066. https://doi.org/10.3402/jev.v4.27066

    Article  PubMed  Google Scholar 

  86. Yang H, Zhang H, Ge S, Ning T, Bai M, Li J, Li S, Sun W, Deng T, Zhang L, Ying G, Ba Y (2018) Exosome-derived miR-130a activates angiogenesis in gastric cancer by targeting C-MYB in vascular endothelial cells. Mol Ther 26(10):2466–2475. https://doi.org/10.1016/j.ymthe.2018.07.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yuana Y, Sturk A, Nieuwland R (2013) Extracellular vesicles in physiological and pathological conditions. Blood Rev 27(1):31–39. https://doi.org/10.1016/j.blre.2012.12.002

    Article  CAS  PubMed  Google Scholar 

  88. Zhang YX, Zhao YY, Shen J, Sun X, Liu Y, Liu H, Wang Y, Wang J (2019) Nanoenabled modulation of acidic tumor microenvironment reverses anergy of infiltrating T cells and potentiates anti-PD-1 therapy. Nano Lett 19(5):2774–2783. https://doi.org/10.1021/acs.nanolett.8b04296

    Article  CAS  PubMed  Google Scholar 

  89. Zheng P, Luo Q, Wang W, Li J, Wang T, Wang P, Chen L, Zhang P, Chen H, Liu Y, Dong P, Xie G, Ma Y, Jiang L, Yuan X, Shen L (2018) Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E. Cell Death Dis 9(4):434. https://doi.org/10.1038/s41419-018-0465-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Zhou J, Li X, Wu X, Zhang T, Zhu Q, Wang X, Wang H, Wang K, Lin Y, Wang X (2018) Exosomes released from tumor-associated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res 6(12):1578–1592. https://doi.org/10.1158/2326-6066.CIR-17-0479

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA

    Alex C. Boomgarden, Colin Sheehan & Crislyn D’Souza-Schorey

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  1. Alex C. Boomgarden
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  2. Colin Sheehan
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Correspondence to Crislyn D’Souza-Schorey .

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  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

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Boomgarden, A.C., Sheehan, C., D’Souza-Schorey, C. (2020). Extracellular Vesicles in the Tumor Microenvironment: Various Implications in Tumor Progression. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1259. Springer, Cham. https://doi.org/10.1007/978-3-030-43093-1_9

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